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*
Institute of Cancer Research and Molecular Biology, Norwegian University of Science and Technology, Trondheim, Norway;
Instituto di Microbiologia, Facolta di Medicina e Chirurgia, Universita degli Studi di Messina, Messina, Italy; and
Department of Medicine, Maxwell Finland Laboratory for Infectious Diseases, Boston Medical Center and Boston University School of Medicine, Boston, MA 02118
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Abstract |
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 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
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B and induction of IL-6 production. A mAb
recognizing a TLR2-associated epitope (TL2.1) was generated that
inhibited IL-6 production from Chinese hamster ovary-TLR2 cells
stimulated with HKLM or LPS. The TL2.1 mAb reduced HKLM-induced TNF
production from human monocytes by 60%, whereas a CD14 mAb (3C10)
reduced the TNF production by 30%. However, coadministrating TL2.1 and
3C10 inhibited the TNF response by 80%. In contrast to this,
anti-CD14 blocked LPS-induced TNF production from monocytes,
whereas anti-TLR2 showed no inhibition. Neither TL2.1 nor 3C10
affected GBS-induced TNF production. These results show that TLR2 can
function as a signaling receptor for HKLM, possibly together with CD14,
but that TLR2 is unlikely to be involved in cell activation by GBS.
Furthermore, although LPS can activate transfected cell lines through
TLR2, this receptor does not seem to be the main transducer of LPS
activation of human monocytes. Thus, our data demonstrate the ability
of TLR2 to distinguish between different
pathogens. |
Introduction |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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The 53- to 55-kDa cell surface glycoprotein CD14 (3) has been identified as the principle LPS-binding molecule on phagocytic leukocytes, enabling them to be stimulated with picogram amounts of LPS (4). CD14 is linked to the membrane with a glycosylphosphatidylinositol anchor (5), and it has been assumed that CD14 mediates LPS activation by interaction with other signal-transducing molecules (6, 7, 8). The recent discovery that human Toll-like receptors (TLRs)3 can signal LPS activation has lent new support to this theory (9, 10, 11, 12, 13).
The Toll protein was first described as the mediator of dorsal-ventral
patterning in Drosophila embryo, and later a role for Toll
and Toll-like proteins in Drosophila innate immunity was
found (14, 15, 16). By now, six human homologues of the
Drosophila Toll have been cloned and designated TLRs 1–6
(17, 18, 19). Like Drosophila Toll, the TLRs are
type I transmembrane proteins with a leucine-rich repeat (LRR)
extracellular domain and a cytoplasmic domain with homology to the
mammalian IL-1R (20). Moreover, as for the IL-1R, NF-B
and related transcription factors can be activated by mammalian and
Drosophila Toll receptors through similar signaling cascades
(20, 21).
Recently, Yang et al. (11) and Kirschning et al.
(10) independently described that TLR2 mediates
LPS-induced NF-B activation when overexpressed in human embryonic
kidney 293 cells. Although these findings suggested that TLR2 may be
the dominant CD14-associated signal transducer in mammalian cells,
subsequent reports demonstrated that the LPS hyporesponsiveness of
C3H/HeJ and C57BL10/ScCr mice maps to a related gene, Tlr4
(9, 22). A Tlr4 knockout mouse has subsequently
been engineered and is similarly hyporesponsive to LPS
(13).
Studies of Drosophila mutants suggest that Toll and homologue receptors discriminate between different pathogens (14, 15, 16). This prompted us to investigate whether TLR2 can function as a signal transducer for two different heat-killed Gram-positive bacteria, Listeria monocytogenes (HKLM) and type III group B streptococci (GBS). GBS is known primarily as the leading cause of sepsis and meningitis in neonates (23). Although several components isolated from GBS employ CD14-dependent pathways in activating cells, whole heat-killed bacteria preferentially use the ß2-integrin CD11b/CD18 (CR3) (M. Cuzzola, et al., manuscript in preparation) (24).
L. monocytogenes is a facultative intracellular bacterium
and the causative agent of food-borne listeriosis. Infections with
L. monocytogenes are rare, but with high rates of mortality,
and the major risk groups are pregnant women, fetuses, neonates, and
immunocompromised individuals (25). Adhesion of L.
monocytogenes to macrophages results in immediate activation of
NF-B and production of proinflammatory cytokines (26).
Both type I scavenger receptor (25) and CD11c/CD18 (CR4)
(M. Cuzzola, et al., manuscript in preparation) have been suggested as
cell receptors for L. monocytogenes, but it is by far still
unclear how it signals cell activation.
In this study, we show that TLR2 mediates cell activation induced by HKLM, but not by GBS, suggesting that human TLR2 distinguishes between two Gram-positive pathogens.
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Materials and Methods |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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LPS (L-2137) from smooth Salmonella minnesota was purchased from Sigma (St. Louis, MO). COH-1, an encapsulated type III GBS strain, was kindly provided by Craig Rubens (University of Washington, Seattle, WA). L. monocytogenes was from a recent clinical isolate. Bacteria were grown to the early stationary phase in Todd-Hewitt broth, killed by heat treatment (60°C for 45 min), washed extensively with distilled water, and lyophilized. Human CD14 mAb 3C10 (IgG2b; American Type Culture Collection, Manassas, VA) and the mAb 6H8 (IgG1) that recognizes a widely distributed 180-kDa glycoprotein (T. Espevik and B. Naume, unpublished observation) were purified from supernatants of the respective hybridoma cell lines on Sepharose goat anti-mouse IgG as described by the manufacturer (Zymed, San Fransisco, CA). Recombinant human TNF (sp. act., 7.6*107 U/mg) was supplied by Genentech (South San Francisco, CA), and recombinant human IL-6 (sp. act., >1*108 U/mg) was purchased from Genzyme (Cambridge, MA).
Cell lines and culture conditions
The following stable, transfected Chinese hamster ovary (CHO)-K1 fibroblast cell lines were generated or have been described elsewhere: CHO-CD14, CHO-K1 transfected with human CD14 (27); CHO-neo, CHO-K1 transfected with pcDNA3/neo (Invitrogen, San Diego, CA); CHO-TLR2 and CHO-TLR4, TLR2 and TLR4 cDNAs cloned into a pFLAG vector (10), gifts from C. Kirschning and M. Rothe (Tularik, San Fransisco, CA), were transfected into CHO-K1 cells along with pcDNA3/neo (28) or pEGFP1/neo (Clontech, Palo Alto, CA), respectively. Stable transfectants were selected by cell sorting and limiting dilution cloning. All transfectants were maintained in RPMI 1640 medium (Life Technologies, Paisley, U.K.) with 0.01% L-glutamine, 40 µg/ml gentamicin (referred to as RPMI), 10% heat-inactivated FCS (HyClone, Logan, UT), and 0.5 mg/ml G418 (Sigma, St. Louis, MO) at 37°C and 5% CO2.
Generation of nuclear extracts and EMSA
Transfected CHO cells were seeded in 6-well plates at a density
of 3 x 105 cells/well and incubated
overnight. Monolayers were then washed twice in HBSS (Life
Technologies) and treated with different stimuli in 1 ml RPMI/2% human
serum (HS) A+ (University Hospital, Trondheim,
Norway) for the indicated period of time. Nuclear extracts were
prepared and analyzed for NF-B-binding activity with a
33P end-labeled NF-B-specific oligonucleotide
probe as described previously (24), except that
autoradiography was performed with a PhosphorImager SF system
(Molecular Dynamics, Sunnyvale, CA). The intensity of the bands was
quantitated by use of ImageQuant software (Sunnyvale, CA), and results
are presented as relative units.
IL-6 assay
CHO cells were plated at a density of 2.5 x 104 cells/well in 24-well dishes. After an overnight incubation, the cells were washed twice with HBSS, and exposed to different stimuli in RPMI/5% HS for 14 h at 37°C. In some experiments, cells were pretreated with 10 µg/ml of a mAb recognizing a TLR2-associated epitope (TL2.1) or a control mAb (6H8) for 30 min at room temperature before addition of the stimuli. Supernatants were collected and stored at -20°C until assayed for IL-6 content by the B9 cell proliferation assay (29). Results from representative experiments are presented as means ± SD of triplicate IL-6 measurements
Generation of a mAb, TL2.1, recognizing a TLR2-associated epitope
Three BALB/c mice (Blomholt Gaard, Denmark) were injected i.p. with 106 CHO-TLR2 cells suspended in 0.5 ml PBS on days 0, 14, and 27. Blood samples were obtained from the thighs on days 0 and 40, and the binding of serum Abs to human PBMC and CHO-TLR2 cells was analyzed by flow cytometry. One mouse was selected and boosted with 106 CHO-TLR2 cells i.p. 4 and 3 days, respectively, before sacrifice. Hybridomas were generated by fusion of mouse spleen cells and NSO myeloma cells (generously provided by Dr. Z. Eshhar, The Weizmann Institute of Science, Rehovot, Israel), and seeded in 96-well plates with hypoxanthine/aminopterin/thymidine selection (30). Hybridoma supernatants were screened for Ab production and specific TLR2 binding by flow cytometry. A hybridoma producing an Ab named TL2.1 (IgG2a) was then subjected to two rounds of limiting dilution cloning to secure monoclonality. TL2.1 was purified on Sepharose goat anti-mouse IgG as described by the manufacturer (Zymed).
Flow cytometry analysis
All steps were performed at 0–4°C. Adherent CHO transfectants were detached by trypsin/0.02% EDTA/PBS, washed twice in PBS/1% heat-inactivated FCS, and incubated with anti-FLAG M2 mAb (Sigma) or PBS/FCS for 45 min. After two washes, the cells were labeled for 30 min with either FITC-conjugated goat anti-mouse mAbs (FITCGAM; Becton Dickinson, Lincoln Park, NJ), a CD14 mAb (FITC-LeuM3; Becton Dickinson), or the TLR2-associated mAb (TL2.1) conjugated to Alexa 488 fluorochrome (Molecular Probes, Eugene, OR). PBMC were isolated from human A+ buffy coats (The Bloodbank, University Hospital, Trondheim, Norway) by Lymfoprep (Nycomed, Oslo, Norway) density gradient centrifugation, which yielded PBMC with <5% contaminating granulocytes. Cells were then washed four times in HBSS and once in PBS/FCS and labeled with Alexa 488-conjugated TL2.1, PE-conjugated CD14 mAb LeuM3 (Becton Dickinson), or both for 30 min. Cells were then washed twice and analyzed with a FACscan flow cytometer (Becton Dickinson).
Metabolic labeling
CHO cells were seeded in 6-well plates and grown to 50–90% confluence. The adherent cells were washed twice with PBS, and labeled with 80–100 µCi TRAN35S-LABEL/well (ICN Pharmaceuticals, Costa Mesa, CA) in methionine- and cysteine-free DMEM (ICN) containing 10% dialyzed FCS for 16 h at 37°C in 8% CO2. All of the subsequent steps were performed at 0–4°C. Cells were washed once in ice-cold PBS and lysed for 10 min with 400 µl lysis buffer/well (50 mM Tris, 150 mM NaCl, 0.1% BSA, 1% Igepal CA630 (Sigma), 0.5 mM PMSF, pH 7.5). Cell lysates were transferred to Eppendorf tubes and spun down at 10,000 x g for 10 min to remove cell debris. The lysates were precleared by incubation with 100 µl Sepharose goat anti-mouse IgG for 30 min, and the supernatants were split into two and immunoprecipitated overnight with 50 µl of either TLR2-associated mAb (TL2.1) or control CD14 mAb (3C10) attached to Sepharose goat anti-mouse IgG (5 µg mAb/1 ml Sepharose). Precipitated samples were washed three times in 50 mM Tris, 0.5 M NaCl, 0.1% BSA, and 0.2% Igepal CA630 (pH 7.5), twice in 50 mM Tris and 0.2% Igepal CA630 (pH 7.5), and separated by SDS gel electrophoresis on an 8% gel. Gels were fixed, incubated in Amplify solution (Amersham, Buckinghamshire, U.K.) for 30 min, and dried before exposure to Kodak MR film (Kodak, Rochester, NY) at -70°C.
Stimulation of monocytes
Adherent cell monolayers (1–2 x 105 monocytes/well in 24-well dishes) were prepared from PBMC as described previously (31). The cells were washed three times in HBSS before addition of 10 µg/ml of TLR2-associated mAb (TL2.1), CD14 mAb (3C10), a combination of TL2.1 and 3C10, or a control mAb (6H8) for 30 min at room temperature in RPMI. After addition of the indicated stimuli, incubation proceeded for 8 h at 37°C before supernatants were collected and stored at -20°C until assayed for TNF activity in the WEHI 164 clone 13 bioassay as described (32). Results from one representative experiment are presented as means ± SD of triplicate TNF measurements.
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Results |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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Recently, CHO-K1 cells were shown to express mRNA encoding a truncated and nonfunctional TLR2 (33). Based on this and recent studies that suggest TLR2 involvement in cellular responses to Gram-positive bacteria (28, 34), we examined the ability of HKLM and GBS to activate CHO cells transfected with human TLR2. CHO-neo, CHO-CD14, and CHO-TLR2 cells were exposed to HKLM, GBS, or LPS for 14 h in the presence of 5% HS, and IL-6 production was measured in supernatants.
As shown in Fig. 1
, LPS induced IL-6
production from CHO-CD14 and CHO-TLR2 cells with similar potency.
Addition of HKLM resulted in IL-6 production from CHO-TLR2 cells, but
not CHO-CD14 cells (Fig. 1). GBS did not induce IL-6 production in
either CHO-TLR2 or in CHO-CD14 cells (Fig. 1). The results indicate
that expression of TLR2, but not CD14, is sufficient for activation of
CHO cells by HKLM, whereas neither TLR2 nor CD14 make CHO cells
responsive to GBS. LPS activates cells in a CD14-dependent manner
(4, 27, 35), and CHO-CD14 cells respond to LPS in the
absence of TLR2 (33). Thus, CD14 or TLR2 are sufficient,
but not necessary, for LPS-induced activation of CHO cells.
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B in CHO-TLR2
cells
In the next series of experiments, CHO-neo and CHO-TLR2 cells were
incubated together with increasing amounts of GBS, HKLM, or LPS for
1 h in the presence of 2% HS before nuclear extracts were
isolated and analyzed for translocation of the transcription factor
NF-B.
As shown in Fig. 2, both HKLM and LPS induced
a dose-dependent NF-B activation of CHO-TLR2 cells. GBS failed to
induce NF-B activation in CHO-TLR2 cells, even at a concentration of
100 µg GBS/ml (Fig. 2). As we have shown that the NF-B response to
GBS cell wall fragments is delayed compared with LPS (24),
we confirmed that GBS did not activate CHO-TLR2 cells at any time
points measured during a 3-h incubation (data not shown). Control
CHO-neo cells were unresponsive to HKLM and GBS, and were
hyporesponsive to LPS, comparable to the data presented in Fig. 1
(data
not shown). These data suggest that TLR2 differs in the way of
recognizing these two types of Gram-positive bacteria.
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To study the biological significance of TLR2 in responses to HKLM,
LPS, and GBS, hybridomas producing mAbs recognizing TLR2-associated
epitopes were generated. The mAb TL2.1 showed profound binding to
CHO-TLR2 cells, but not to CHO-neo, CHO-CD14, or CHO-TLR4 cells (Fig. 3A) suggesting that this mAb
specifically recognizes a TLR2-associated epitope. Controls with mAbs
to the FLAG-tag or to CD14 confirmed that the cells expressed
FLAG-TLR2, FLAG-TLR4, or CD14, respectively, and the lack of binding of
TL2.1 to CHO-TLR4 cells further indicate that TL2.1 is not directed
toward the FLAG epitope.
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, one protein band of 
98 kDa appeared
only in the CHO-TLR2 lysate immunoprecipitated with TL2.1. The same
98-kDa band was obtained from CHO-TLR2 cells, but not CHO-neo or
CHO-TLR4 cells, when TL2.1 immunoprecipitates were subjected to Western
blot and detection with biotinylated anti-FLAG mAb (data not
shown). We further compared the expression of the TL2.1-defined epitope
and CD14 on PBMC by incubating PBMC with Alexa 488-labeled TL2.1 and a
PE-labeled CD14 mAb (LeuM3). As shown in Fig. 3B, TL2.1
colocalized with LeuM3 and <2% of the PBMC were
TL2.1+/LeuM3-. Thus, in
PBMC the expression of the TLR2-associated epitope defined by TL2.1 is
mainly restricted to monocytes, reinforcing the assumptions that TLR2
serves a role in human innate immunity.
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To examine the ability of TL2.1 to specifically block
TLR2-mediated cell activation, CHO-TLR2 and CHO-CD14 cells were
pretreated with TL2.1 or a control mAb (6H8) before addition of HKLM or
LPS. Results in Fig. 5 show that TL2.1
inhibited both HKLM- and LPS-induced IL-6 production from CHO-TLR2
cells with about 60%, but had no inhibiting effect on the LPS-induced
activation of CHO-CD14 cells. The control mAb, 6H8, did not affect the
IL-6 production induced in either cell transfectants. These data show
that the TL2.1 mAb interacts with a TLR2 epitope that is involved in
HKLM and LPS signaling in CHO-TLR2 cells.
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In the next experiments, we studied the inhibitory action of the
TLR2-associated mAb (TL2.1) and a CD14 mAb (3C10) on TNF production
from human monocytes stimulated with HKLM, GBS, or LPS at serum-free
conditions. Both TL2.1 and, to a lesser extent, 3C10, independently
inhibited HKLM-induced TNF production, but combining the two mAbs was
more effective in blocking the response than adding them individually
(Fig. 6). The data indicate that both CD14
and TLR2 are involved in mediating HKLM-induced TNF production from
monocytes. Neither TL2.1 nor 3C10 inhibited the GBS-induced TNF
production from monocytes (data not shown), which confirms the earlier
observations that different mechanisms mediate cell activation by HKLM
and GBS.
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Discussion |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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The Gram-positive bacterial surface is composed of similar structures like teichoic acids, lipoteichoic acids (LTA), and the cell wall peptidoglycan, but also dissimilar polysaccharides and proteins (36). Thus, even if common Gram-positive structures activate cells through the same pathways, as the CD14-mediated stimulation by LTA (37) and peptidoglycan (38, 39, 40), the signaling mechanism used by whole bacteria can differ according to the complex surface expression of proteins and carbohydrates. This is different from most Gram-negative bacteria, where LPS clearly is the dominant surface component.
TLR2 or CD14 did not mediate GBS-induced activation of either CHO cells or human monocytes. These results are in sharp contrast to TLR2-mediated cellular activation demonstrated in response to HKLM and other Gram-positive organisms, such as Staphylococcus aureus and Streptococcus pneumoniae (28). We and others have found that GBS use a CR3-dependent pathway to stimulate TNF production from monocytes (M. Cuzzola, et al., manuscript in preparation) (24, 41). Thus, CR3 may serve to bring GBS in closer contact with putative signal transducers similar to CD14 in responses to LPS. The results from this study indicate that TLR2 is not the GBS signal transducer, and as the LPS hyporesponsive and TLR4-defective C3H/HeJ mice respond normally to GBS (24), the identity of the GBS-signaling component(s) remains to be found.
By use of blocking mAbs to a TLR2-associated epitope and CD14, we demonstrated that HKLM used CD14 and TLR2 to induce TNF production from human monocytes. HKLM differ from GBS in cellular composition. Whereas group- and type-specific polysaccharides cover the encapsulated GBS surface, it has been proposed that HKLM adhere to mammalian cells by proteins called internalins and/or by LTA (25). Abs against CD14 may inhibit the subsequent interaction of LTA on HKLM with TLR2 on the monocytes. The results that expression of CD14 on CHO cells was insufficient to signal cell activation by HKLM could be due to the inability of TLR2 to induce cell activation in these cells (33). Recently, the MD-2 molecule was shown to confer LPS responsiveness by physical association with TLR4 (42). Both MD-2 and TLR4 contain extracellular LRRs, and the possibility exists that CD14 interacts with TLR2 through their LRRs to mediate HKLM signaling. On the other hand, we cannot exclude that TL2.1 and the anti-CD14 mAb inhibited separate pathways in monocytes activated by HKLM.
Both HKLM- and LPS-induced activation of CHO-TLR2 cells was inhibited by the TL2.1 mAb. In contrast to this, TL2.1 failed to inhibit LPS-induced TNF production from human monocytes. However, it cannot be ruled out that other types of LPS than the one used in this study may activate monocytes through TLR2. Recently, Brightbill et al. (43) showed that a TLR2 mAb could inhibit IL-12 production from human monocytes stimulated with LPS from Salmonella typhosa. LPS activation through TLR2 has mostly been studied in transfected cell lines (10, 11), and our results indicate that this is not necessarily the main pathway of LPS-induced TNF production in monocytes. TLR4 is a strong candidate as a LPS signal transducer in normal phagocytes, as Tlr4-mutant or knockout mice show hyporesponsiveness to LPS (9, 13, 22). In addition, TLR4-expressing cell lines become LPS responsive by MD-2 transfection (42).
Our study shows that human TLR2 discriminates between different pathogens. It remains to be shown, however, whether microbial components are true TLR ligands, whether they bind accessory receptor molecules like MD-2 (42), or whether the ligands are generated by some proteolytic cascade initiated by the pathogen (14).
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Footnotes |
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2 Address correspondence and reprint requests to Dr. Terje Espevik, Institute of Cancer Research and Molecular Biology, Norwegian University of Science and Technology, 7489 Trondheim, Norway. E-mail address:
3 Abbreviations used in this paper: TLR, Toll-like receptor; LRR, leucine-rich repeat; HKLM, heat-killed Listeria monocytogenes; GBS, group B streptococci type III; CHO, Chinese hamster ovary; HS, normal human serum A+; LTA, lipoteichoic acid.
Received for publication August 5, 1999. Accepted for publication December 3, 1999.
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References |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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B activation and TNF production induced by lipopolysaccharide and group B streptococcal cell walls. J. Immunol. 160:4535.B (RelA/p50) activation induced by lipoteichoic acid and bacterial phospholipases and mediated by IB
and IBß degradation. Proc. Natl. Acad. Sci. USA 94:9394.This article has been cited by other articles:
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G. Mancuso, A. Midiri, C. Biondo, C. Beninati, M. Gambuzza, D. Macri, A. Bellantoni, A. Weintraub, T. Espevik, and G. Teti Bacteroides fragilis-Derived Lipopolysaccharide Produces Cell Activation and Lethal Toxicity via Toll-Like Receptor 4 Infect. Immun., September 1, 2005; 73(9): 5620 - 5627. [Abstract] [Full Text] [PDF]
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B. Schmeck, W. Beermann, V. van Laak, J. Zahlten, B. Opitz, M. Witzenrath, A. C. Hocke, T. Chakraborty, M. Kracht, S. Rosseau, et al. Intracellular Bacteria Differentially Regulated Endothelial Cytokine Release by MAPK-Dependent Histone Modification J. Immunol., September 1, 2005; 175(5): 2843 - 2850. [Abstract] [Full Text] [PDF]
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P. Henneke, S. Morath, S. Uematsu, S. Weichert, M. Pfitzenmaier, O. Takeuchi, A. Muller, C. Poyart, S. Akira, R. Berner, et al. Role of Lipoteichoic Acid in the Phagocyte Response to Group B Streptococcus J. Immunol., May 15, 2005; 174(10): 6449 - 6455. [Abstract] [Full Text] [PDF]
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S. Braedel-Ruoff, M. Faigle, N. Hilf, B. Neumeister, and H. Schild Legionella pneumophila mediated activation of dendritic cells involves CD14 and TLR2 Innate Immunity, April 1, 2005; 11(2): 89 - 96. [Abstract] [PDF]
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G. Tunheim, K. W. Schjetne, A. B. Fredriksen, I. Sandlie, and B. Bogen Human CD14 is an efficient target for recombinant immunoglobulin vaccine constructs that deliver T cell epitopes J. Leukoc. Biol., March 1, 2005; 77(3): 303 - 310. [Abstract] [Full Text] [PDF]
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S. Stockinger, B. Reutterer, B. Schaljo, C. Schellack, S. Brunner, T. Materna, M. Yamamoto, S. Akira, T. Taniguchi, P. J. Murray, et al. IFN Regulatory Factor 3-Dependent Induction of Type I IFNs by Intracellular Bacteria Is Mediated by a TLR- and Nod2-Independent Mechanism J. Immunol., December 15, 2004; 173(12): 7416 - 7425. [Abstract] [Full Text] [PDF]
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N. Nilsen, U. Nonstad, N. Khan, C. F. Knetter, S. Akira, A. Sundan, T. Espevik, and E. Lien Lipopolysaccharide and Double-stranded RNA Up-regulate Toll-like Receptor 2 Independently of Myeloid Differentiation Factor 88 J. Biol. Chem., September 17, 2004; 279(38): 39727 - 39735. [Abstract] [Full Text] [PDF]
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A. M. Firoved, W. Ornatowski, and V. Deretic Microarray Analysis Reveals Induction of Lipoprotein Genes in Mucoid Pseudomonas aeruginosa: Implications for Inflammation in Cystic Fibrosis Infect. Immun., September 1, 2004; 72(9): 5012 - 5018. [Abstract] [Full Text] [PDF]
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 J. Oestvang, D. Bonnefont-Rousselot, E. Ninio, J. K. Hakala, B. Johansen, and M. W. Anthonsen Modification of LDL with human secretory phospholipase A2 or sphingomyelinase promotes its arachidonic acid-releasing propensity J. Lipid Res., May 1, 2004; 45(5): 831 - 838. [Abstract] [Full Text] [PDF]
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D. Torres, M. Barrier, F. Bihl, V. J. F. Quesniaux, I. Maillet, S. Akira, B. Ryffel, and F. Erard Toll-Like Receptor 2 Is Required for Optimal Control of Listeria monocytogenes Infection Infect. Immun., April 1, 2004; 72(4): 2131 - 2139. [Abstract] [Full Text] [PDF]
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 H.-J. Anders, B. Banas, and D. Schlondorff Signaling Danger: Toll-Like Receptors and their Potential Roles in Kidney Disease J. Am. Soc. Nephrol., April 1, 2004; 15(4): 854 - 867. [Abstract] [Full Text] [PDF]
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M. Komai-Koma, L. Jones, G. S. Ogg, D. Xu, and F. Y. Liew TLR2 is expressed on activated T cells as a costimulatory receptor PNAS, March 2, 2004; 101(9): 3029 - 3034. [Abstract] [Full Text] [PDF]
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T. Okusawa, M. Fujita, J.-i. Nakamura, T. Into, M. Yasuda, A. Yoshimura, Y. Hara, A. Hasebe, D. T. Golenbock, M. Morita, et al. Relationship between Structures and Biological Activities of Mycoplasmal Diacylated Lipopeptides and Their Recognition by Toll-Like Receptors 2 and 6 Infect. Immun., March 1, 2004; 72(3): 1657 - 1665. [Abstract] [Full Text] [PDF]
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E. Latz, J. Franko, D. T. Golenbock, and J. R. Schreiber Haemophilus influenzae Type b-Outer Membrane Protein Complex Glycoconjugate Vaccine Induces Cytokine Production by Engaging Human Toll-Like Receptor 2 (TLR2) and Requires the Presence of TLR2 for Optimal Immunogenicity J. Immunol., February 15, 2004; 172(4): 2431 - 2438. [Abstract] [Full Text] [PDF]
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H. Zhou, H. Xiong, H. Li, S. E. Plevy, P. D. Walden, M. Sassaroli, G. D. Prestwich, and J. C. Unkeless Microtubule-Associated Serine/Threonine Kinase-205 kDa and Fc{gamma} Receptor Control IL-12 p40 Synthesis and NF-{kappa}B Activation J. Immunol., February 15, 2004; 172(4): 2559 - 2568. [Abstract] [Full Text] [PDF]
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M. Galdiero, M. Galdiero, E. Finamore, F. Rossano, M. Gambuzza, M. R. Catania, G. Teti, A. Midiri, and G. Mancuso Haemophilus influenzae Porin Induces Toll-Like Receptor 2-Mediated Cytokine Production in Human Monocytes and Mouse Macrophages Infect. Immun., February 1, 2004; 72(2): 1204 - 1209. [Abstract] [Full Text] [PDF]
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N. M. Tsuji, H. Tsutsui, E. Seki, K. Kuida, H. Okamura, K. Nakanishi, and R. A. Flavell Roles of caspase-1 in Listeria infection in mice Int. Immunol., February 1, 2004; 16(2): 335 - 343. [Abstract] [Full Text] [PDF]
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A.-S. W. Moller, R. Ovstebo, A.-B. Westvik, G. B. Joo, K.-B. F. Haug, and P. Kierulf Effects of bacterial cell wall components (PAMPs) on the expression of monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1{alpha} (MIP-1{alpha}) and the chemokine receptor CCR2 by purified human blood monocytes Innate Immunity, December 1, 2003; 9(6): 349 - 360. [Abstract] [PDF]
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O. Levy, R. M. Jean-Jacques, C. Cywes, R. B. Sisson, K. A. Zarember, P. J. Godowski, J. L. Christianson, H.-K. Guttormsen, M. C. Carroll, A. Nicholson-Weller, et al. Critical Role of the Complement System in Group B Streptococcus-Induced Tumor Necrosis Factor Alpha Release Infect. Immun., November 1, 2003; 71(11): 6344 - 6353. [Abstract] [Full Text] [PDF]
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J. L. Coleman and J. L. Benach The Urokinase Receptor Can Be Induced by Borrelia burgdorferi through Receptors of the Innate Immune System Infect. Immun., October 1, 2003; 71(10): 5556 - 5564. [Abstract] [Full Text] [PDF]
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 Y. Tsunetsugu-Yokota, Y. Morikawa, M. Isogai, A. Kawana-Tachikawa, T. Odawara, T. Nakamura, F. Grassi, B. Autran, and A. Iwamoto Yeast-Derived Human Immunodeficiency Virus Type 1 p55gag Virus-Like Particles Activate Dendritic Cells (DCs) and Induce Perforin Expression in Gag-Specific CD8+ T Cells by Cross-Presentation of DCs J. Virol., October 1, 2003; 77(19): 10250 - 10259. [Abstract] [Full Text] [PDF]
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M. Fujita, T. Into, M. Yasuda, T. Okusawa, S. Hamahira, Y. Kuroki, A. Eto, T. Nisizawa, M. Morita, and K.-i. Shibata Involvement of Leucine Residues at Positions 107, 112, and 115 in a Leucine-Rich Repeat Motif of Human Toll-Like Receptor 2 in the Recognition of Diacylated Lipoproteins and Lipopeptides and Staphylococcus aureus Peptidoglycans J. Immunol., October 1, 2003; 171(7): 3675 - 3683. [Abstract] [Full Text] [PDF]
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J. Uehori, M. Matsumoto, S. Tsuji, T. Akazawa, O. Takeuchi, S. Akira, T. Kawata, I. Azuma, K. Toyoshima, and T. Seya Simultaneous Blocking of Human Toll-Like Receptors 2 and 4 Suppresses Myeloid Dendritic Cell Activation Induced by Mycobacterium bovis Bacillus Calmette-Guerin Peptidoglycan Infect. Immun., August 1, 2003; 71(8): 4238 - 4249. [Abstract] [Full Text] [PDF]
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H. M. Paterson, T. J. Murphy, E. J. Purcell, O. Shelley, S. J. Kriynovich, E. Lien, J. A. Mannick, and J. A. Lederer Injury Primes the Innate Immune System for Enhanced Toll-Like Receptor Reactivity J. Immunol., August 1, 2003; 171(3): 1473 - 1483. [Abstract] [Full Text] [PDF]
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 S. Nakahara, T. Tsunoda, T. Baba, S. Asabe, and H. Tahara Dendritic Cells Stimulated with a Bacterial Product, OK-432, Efficiently Induce Cytotoxic T Lymphocytes Specific to Tumor Rejection Peptide Cancer Res., July 15, 2003; 63(14): 4112 - 4118. [Abstract] [Full Text] [PDF]
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S. S. Way, T. R. Kollmann, A. M. Hajjar, and C. B. Wilson Cutting Edge: Protective Cell-Mediated Immunity to Listeria monocytogenes in the Absence of Myeloid Differentiation Factor 88 J. Immunol., July 15, 2003; 171(2): 533 - 537. [Abstract] [Full Text] [PDF]
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 M. Adib-Conquy, P. Moine, K. Asehnoune, A. Edouard, T. Espevik, K. Miyake, C. Werts, and J.-M. Cavaillon Toll-like Receptor-mediated Tumor Necrosis Factor and Interleukin-10 Production Differ during Systemic Inflammation Am. J. Respir. Crit. Care Med., July 15, 2003; 168(2): 158 - 164. [Abstract] [Full Text] [PDF]
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K. W. Schjetne, K. M. Thompson, N. Nilsen, T. H. Flo, B. Fleckenstein, J.-G. Iversen, T. Espevik, and B. Bogen Cutting Edge: Link Between Innate and Adaptive Immunity: Toll-Like Receptor 2 Internalizes Antigen for Presentation to CD4+ T Cells and Could Be an Efficient Vaccine Target J. Immunol., July 1, 2003; 171(1): 32 - 36. [Abstract] [Full Text] [PDF]
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J. H. M. Levels, P. R. Abraham, E. P. van Barreveld, J. C. M. Meijers, and S. J. H. van Deventer Distribution and Kinetics of Lipoprotein-Bound Lipoteichoic Acid Infect. Immun., June 1, 2003; 71(6): 3280 - 3284. [Abstract] [Full Text] [PDF]
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I. Sabroe, L. R. Prince, E. C. Jones, M. J. Horsburgh, S. J. Foster, S. N. Vogel, S. K. Dower, and M. K. B. Whyte Selective Roles for Toll-Like Receptor (TLR)2 and TLR4 in the Regulation of Neutrophil Activation and Life Span J. Immunol., May 15, 2003; 170(10): 5268 - 5275. [Abstract] [Full Text] [PDF]
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 R. Girard, T. Pedron, S. Uematsu, V. Balloy, M. Chignard, S. Akira, and R. Chaby Lipopolysaccharides from Legionella and Rhizobium stimulate mouse bone marrow granulocytes via Toll-like receptor 2 J. Cell Sci., January 15, 2003; 116(2): 293 - 302. [Abstract] [Full Text] [PDF]
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D. van der Kleij, E. Latz, J. F. H. M. Brouwers, Y. C. M. Kruize, M. Schmitz, E. A. Kurt-Jones, T. Espevik, E. C. de Jong, M. L. Kapsenberg, D. T. Golenbock, et al. A Novel Host-Parasite Lipid Cross-talk. SCHISTOSOMAL LYSO-PHOSPHATIDYLSERINE ACTIVATES TOLL-LIKE RECEPTOR 2 AND AFFECTS IMMUNE POLARIZATION J. Biol. Chem., December 6, 2002; 277(50): 48122 - 48129. [Abstract] [Full Text] [PDF]
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A. E. Medvedev, A. Lentschat, L. M. Wahl, D. T. Golenbock, and S. N. Vogel Dysregulation of LPS-Induced Toll-Like Receptor 4-MyD88 Complex Formation and IL-1 Receptor-Associated Kinase 1 Activation in Endotoxin-Tolerant Cells J. Immunol., November 1, 2002; 169(9): 5209 - 5216. [Abstract] [Full Text] [PDF]
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S. S. Mambula, K. Sau, P. Henneke, D. T. Golenbock, and S. M. Levitz Toll-like Receptor (TLR) Signaling in Response to Aspergillus fumigatus J. Biol. Chem., October 11, 2002; 277(42): 39320 - 39326. [Abstract] [Full Text] [PDF]
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E. Seki, H. Tsutsui, N. M. Tsuji, N. Hayashi, K. Adachi, H. Nakano, S. Futatsugi-Yumikura, O. Takeuchi, K. Hoshino, S. Akira, et al. Critical Roles of Myeloid Differentiation Factor 88-Dependent Proinflammatory Cytokine Release in Early Phase Clearance of Listeria monocytogenes in Mice J. Immunol., October 1, 2002; 169(7): 3863 - 3868. [Abstract] [Full Text] [PDF]
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B. T. Edelson and E. R. Unanue MyD88-Dependent but Toll-Like Receptor 2-Independent Innate Immunity to Listeria: No Role for Either in Macrophage Listericidal Activity J. Immunol., October 1, 2002; 169(7): 3869 - 3875. [Abstract] [Full Text] [PDF]
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P. Henneke, O. Takeuchi, R. Malley, E. Lien, R. R. Ingalls, M. W. Freeman, T. Mayadas, V. Nizet, S. Akira, D. L. Kasper, et al. Cellular Activation, Phagocytosis, and Bactericidal Activity Against Group B Streptococcus Involve Parallel Myeloid Differentiation Factor 88-Dependent and Independent Signaling Pathways J. Immunol., October 1, 2002; 169(7): 3970 - 3977. [Abstract] [Full Text] [PDF]
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T. H. Flo, L. Ryan, E. Latz, O. Takeuchi, B. G. Monks, E. Lien, O. Halaas, S. Akira, G. Skjak-Brak, D. T. Golenbock, et al. Involvement of Toll-like Receptor (TLR) 2 and TLR4 in Cell Activation by Mannuronic Acid Polymers J. Biol. Chem., September 13, 2002; 277(38): 35489 - 35495. [Abstract] [Full Text] [PDF]
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 E. A. Kurt-Jones, L. Mandell, C. Whitney, A. Padgett, K. Gosselin, P. E. Newburger, and R. W. Finberg Role of Toll-like receptor 2 (TLR2) in neutrophil activation: GM-CSF enhances TLR2 expression and TLR2-mediated interleukin 8 responses in neutrophils Blood, August 13, 2002; 100(5): 1860 - 1868. [Abstract] [Full Text] [PDF]
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S. H. Gregory and E. J. Wing Neutrophil-Kupffer cell interaction: a critical component of host defenses to systemic bacterial infections J. Leukoc. Biol., August 1, 2002; 72(2): 239 - 248. [Abstract] [Full Text] [PDF]
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 A. UEHARA, S. SUGAWARA, and H. TAKADA Priming of human oral epithelial cells by interferon-{gamma} to secrete cytokines in response to lipopolysaccharides, lipoteichoic acids and peptidoglycans J. Med. Microbiol., August 1, 2002; 51(8): 626 - 634. [Abstract] [Full Text] [PDF]
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G. Mancuso, A. Midiri, C. Beninati, G. Piraino, A. Valenti, G. Nicocia, D. Teti, J. Cook, and G. Teti Mitogen-Activated Protein Kinases and NF-{kappa}B Are Involved in TNF-{alpha} Responses to Group B Streptococci J. Immunol., August 1, 2002; 169(3): 1401 - 1409. [Abstract] [Full Text] [PDF]
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K. Bieback, E. Lien, I. M. Klagge, E. Avota, J. Schneider-Schaulies, W. P. Duprex, H. Wagner, C. J. Kirschning, V. ter Meulen, and S. Schneider-Schaulies Hemagglutinin Protein of Wild-Type Measles Virus Activates Toll-Like Receptor 2 Signaling J. Virol., July 29, 2002; 76(17): 8729 - 8736. [Abstract] [Full Text] [PDF]
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V. Haehnel, L. Schwarzfischer, M. J. Fenton, and M. Rehli Transcriptional Regulation of the Human Toll-Like Receptor 2 Gene in Monocytes and Macrophages J. Immunol., June 1, 2002; 168(11): 5629 - 5637. [Abstract] [Full Text] [PDF]
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M. D. Lehner, F. Schwoebel, A. Kotlyarov, M. Leist, M. Gaestel, and T. Hartung Mitogen-Activated Protein Kinase-Activated Protein Kinase 2-Deficient Mice Show Increased Susceptibility to Listeria monocytogenes Infection J. Immunol., May 1, 2002; 168(9): 4667 - 4673. [Abstract] [Full Text] [PDF]
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H.-K. Lee, J. Lee, and P. S. Tobias Two Lipoproteins Extracted from Escherichia coli K-12 LCD25 Lipopolysaccharide Are the Major Components Responsible for Toll-Like Receptor 2-Mediated Signaling J. Immunol., April 15, 2002; 168(8): 4012 - 4017. [Abstract] [Full Text] [PDF]
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 R. Berner, B. Furll, F. Stelter, J. Drose, H.-P. Muller, and C. Schutt Elevated Levels of Lipopolysaccharide-Binding Protein and Soluble CD14 in Plasma in Neonatal Early-Onset Sepsis Clin. Vaccine Immunol., March 1, 2002; 9(2): 440 - 445. [Abstract] [Full Text] [PDF]
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T. Vasselon and P. A. Detmers Toll Receptors: a Central Element in Innate Immune Responses Infect. Immun., March 1, 2002; 70(3): 1033 - 1041. [Full Text] [PDF]
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R. Tamai, T. Sakuta, K. Matsushita, M. Torii, O. Takeuchi, S. Akira, S. Akashi, T. Espevik, S. Sugawara, and H. Takada Human Gingival CD14+ Fibroblasts Primed with Gamma Interferon Increase Production of Interleukin-8 in Response to Lipopolysaccharide through Up-Regulation of Membrane CD14 and MyD88 mRNA Expression Infect. Immun., March 1, 2002; 70(3): 1272 - 1278. [Abstract] [Full Text] [PDF]
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A. Fox-Marsh and L. C. Harrison Emerging evidence that molecules expressed by mammalian tissue grafts are recognized by the innate immune system J. Leukoc. Biol., March 1, 2002; 71(3): 401 - 409. [Abstract] [Full Text] [PDF]
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R. N. Fichorova, A. O. Cronin, E. Lien, D. J. Anderson, and R. R. Ingalls Response to Neisseria gonorrhoeae by Cervicovaginal Epithelial Cells Occurs in the Absence of Toll-Like Receptor 4-Mediated Signaling J. Immunol., March 1, 2002; 168(5): 2424 - 2432. [Abstract] [Full Text] [PDF]
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P. Massari, P. Henneke, Y. Ho, E. Latz, D. T. Golenbock, and L. M. Wetzler Cutting Edge: Immune Stimulation by Neisserial Porins Is Toll-Like Receptor 2 and MyD88 Dependent J. Immunol., February 15, 2002; 168(4): 1533 - 1537. [Abstract] [Full Text] [PDF]
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T. Wang, W. P. Lafuse, and B. S. Zwilling NF{kappa}B and Sp1 Elements Are Necessary for Maximal Transcription of Toll-like Receptor 2 Induced by Mycobacterium avium J. Immunol., December 15, 2001; 167(12): 6924 - 6932. [Abstract] [Full Text] [PDF]
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P. Henneke, O. Takeuchi, J. A. van Strijp, H.-K. Guttormsen, J. A. Smith, A. B. Schromm, T. A. Espevik, S. Akira, V. Nizet, D. L. Kasper, et al. Novel Engagement of CD14 and Multiple Toll-Like Receptors by Group B Streptococci J. Immunol., December 15, 2001; 167(12): 7069 - 7076. [Abstract] [Full Text] [PDF]
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H.-W. Mittrucker, M. Kursar, A. Kohler, R. Hurwitz, and S. H. E. Kaufmann Role of CD28 for the Generation and Expansion of Antigen-Specific CD8+ T Lymphocytes During Infection with Listeria monocytogenes J. Immunol., November 15, 2001; 167(10): 5620 - 5627. [Abstract] [Full Text] [PDF]
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S. Prebeck, C. Kirschning, S. Durr, C. da Costa, B. Donath, K. Brand, V. Redecke, H. Wagner, and T. Miethke Predominant Role of Toll-Like Receptor 2 Versus 4 in Chlamydia pneumoniae-Induced Activation of Dendritic Cells J. Immunol., September 15, 2001; 167(6): 3316 - 3323. [Abstract] [Full Text] [PDF]
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S. Sugawara, S. Yang, K. Iki, J. Hatakeyama, R. Tamai, O. Takeuchi, S. Akashi, T. Espevik, S. Akira, and H. Takada Monocytic Cell Activation by Nonendotoxic Glycoprotein from Prevotella intermedia ATCC 25611 Is Mediated by Toll-Like Receptor 2 Infect. Immun., August 1, 2001; 69(8): 4951 - 4957. [Abstract] [Full Text] [PDF]
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L. Rabehi, T. Irinopoulou, B. Cholley, N. Haeffner-Cavaillon, and M.-P. Carreno Gram-Positive and Gram-Negative Bacteria Do Not Trigger Monocytic Cytokine Production through Similar Intracellular Pathways Infect. Immun., July 1, 2001; 69(7): 4590 - 4599. [Abstract] [Full Text] [PDF]
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H.-H. Mu, A. D. Sawitzke, and B. C. Cole Presence of Lpsd Mutation Influences Cytokine Regulation In Vivo by the Mycoplasma arthritidis Mitogen Superantigen and Lethal Toxicity in Mice Infected with M. arthritidis Infect. Immun., June 1, 2001; 69(6): 3837 - 3844. [Abstract] [Full Text] [PDF]
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B. W. Jones, T. K. Means, K. A. Heldwein, M. A. Keen, P. J. Hill, J. T. Belisle, and M. J. Fenton Different Toll-like receptor agonists induce distinct macrophage responses J. Leukoc. Biol., June 1, 2001; 69(6): 1036 - 1044. [Abstract] [Full Text] [PDF]
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Y. Liu, Y. Wang, M. Yamakuchi, S. Isowaki, E. Nagata, Y. Kanmura, I. Kitajima, and I. Maruyama Upregulation of Toll-Like Receptor 2 Gene Expression in Macrophage Response to Peptidoglycan and High Concentration of Lipopolysaccharide Is Involved in NF-{kappa}B Activation Infect. Immun., May 1, 2001; 69(5): 2788 - 2796. [Abstract] [Full Text] [PDF]
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M. D. Lehner, S. Morath, K. S. Michelsen, R. R. Schumann, and T. Hartung Induction of Cross-Tolerance by Lipopolysaccharide and Highly Purified Lipoteichoic Acid Via Different Toll-Like Receptors Independent of Paracrine Mediators J. Immunol., April 15, 2001; 166(8): 5161 - 5167. [Abstract] [Full Text] [PDF]
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R. R. Ingalls, E. Lien, and D. T. Golenbock Membrane-Associated Proteins of a Lipopolysaccharide-Deficient Mutant of Neisseria meningitidis Activate the Inflammatory Response through Toll-Like Receptor 2 Infect. Immun., April 1, 2001; 69(4): 2230 - 2236. [Abstract] [Full Text] [PDF]
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J. E. Wang, A. Warris, E. A. Ellingsen, P. F. Jorgensen, T. H. Flo, T. Espevik, R. Solberg, P. E. Verweij, and A. O. Aasen Involvement of CD14 and Toll-Like Receptors in Activation of Human Monocytes by Aspergillus fumigatus Hyphae Infect. Immun., April 1, 2001; 69(4): 2402 - 2406. [Abstract] [Full Text] [PDF]
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T. Kielian, B. Barry, and W. F. Hickey CXC Chemokine Receptor-2 Ligands Are Required for Neutrophil-Mediated Host Defense in Experimental Brain Abscesses1 J. Immunol., April 1, 2001; 166(7): 4634 - 4643. [Abstract] [Full Text] [PDF]
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T. H. Flo, O. Halaas, S. Torp, L. Ryan, E. Lien, B. Dybdahl, A. Sundan, and T. Espevik Differential expression of Toll-like receptor 2 in human cells J. Leukoc. Biol., March 1, 2001; 69(3): 474 - 481. [Abstract] [Full Text]
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E. Seki, H. Tsutsui, H. Nakano, N. M. Tsuji, K. Hoshino, O. Adachi, K. Adachi, S. Futatsugi, K. Kuida, O. Takeuchi, et al. Lipopolysaccharide-Induced IL-18 Secretion from Murine Kupffer Cells Independently of Myeloid Differentiation Factor 88 That Is Critically Involved in Induction of Production of IL-12 and IL-1{{beta}} J. Immunol., February 15, 2001; 166(4): 2651 - 2657. [Abstract] [Full Text] [PDF]
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E. Faure, L. Thomas, H. Xu, A. E. Medvedev, O. Equils, and M. Arditi Bacterial Lipopolysaccharide and IFN-{{gamma}} Induce Toll-Like Receptor 2 and Toll-Like Receptor 4 Expression in Human Endothelial Cells: Role of NF-{{kappa}}B Activation J. Immunol., February 1, 2001; 166(3): 2018 - 2024. [Abstract] [Full Text] [PDF]
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A. M. Hajjar, D. S. O'Mahony, A. Ozinsky, D. M. Underhill, A. Aderem, S. J. Klebanoff, and C. B. Wilson Cutting Edge: Functional Interactions Between Toll-Like Receptor (TLR) 2 and TLR1 or TLR6 in Response to Phenol-Soluble Modulin J. Immunol., January 1, 2001; 166(1): 15 - 19. [Abstract] [Full Text] [PDF]
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T. H. Flo, L. Ryan, L. Kilaas, G. Skjak-Brak, R. R. Ingalls, A. Sundan, D. T. Golenbock, and T. Espevik Involvement of CD14 and beta 2-Integrins in Activating Cells with Soluble and Particulate Lipopolysaccharides and Mannuronic Acid Polymers Infect. Immun., December 1, 2000; 68(12): 6770 - 6776. [Abstract] [Full Text] [PDF]
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T. Wang, W. P. Lafuse, and B. S. Zwilling Regulation of Toll-Like Receptor 2 Expression by Macrophages Following Mycobacterium avium Infection J. Immunol., December 1, 2000; 165(11): 6308 - 6313. [Abstract] [Full Text] [PDF]
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R. I. Tapping, S. Akashi, K. Miyake, P. J. Godowski, and P. S. Tobias Toll-Like Receptor 4, But Not Toll-Like Receptor 2, Is a Signaling Receptor for Escherichia and Salmonella Lipopolysaccharides J. Immunol., November 15, 2000; 165(10): 5780 - 5787. [Abstract] [Full Text] [PDF]
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E. Lorenz, J. P. Mira, K. L. Cornish, N. C. Arbour, and D. A. Schwartz A Novel Polymorphism in the Toll-Like Receptor 2 Gene and Its Potential Association with Staphylococcal Infection Infect. Immun., November 1, 2000; 68(11): 6398 - 6401. [Abstract] [Full Text] [PDF]
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R. R. Ingalls, E. Lien, and D. T. Golenbock Differential roles of TLR2 and TLR4 in the host response to Gram-negative bacteria: lessons from a lipopolysaccharide-deficient mutant of Neisseria meningitidis Innate Immunity, October 1, 2000; 6(5): 411 - 415. [Abstract] [PDF]
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S. Thoma-Uszynski, S. M. Kiertscher, M. T. Ochoa, D. A. Bouis, M. V. Norgard, K. Miyake, P. J. Godowski, M. D. Roth, and R. L. Modlin Activation of Toll-Like Receptor 2 on Human Dendritic Cells Triggers Induction of IL-12, But Not IL-10 J. Immunol., October 1, 2000; 165(7): 3804 - 3810. [Abstract] [Full Text] [PDF]
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M. Hirschfeld, Y. Ma, J. H. Weis, S. N. Vogel, and J. J. Weis Cutting Edge: Repurification of Lipopolysaccharide Eliminates Signaling Through Both Human and Murine Toll-Like Receptor 2 J. Immunol., July 15, 2000; 165(2): 618 - 622. [Abstract] [Full Text] [PDF]
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E. Lien, J. C. Chow, L. D. Hawkins, P. D. McGuinness, K. Miyake, T. Espevik, F. Gusovsky, and D. T. Golenbock A Novel Synthetic Acyclic Lipid A-like Agonist Activates Cells via the Lipopolysaccharide/Toll-like Receptor 4 Signaling Pathway J. Biol. Chem., January 12, 2001; 276(3): 1873 - 1880. [Abstract] [Full Text] [PDF]
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J. da Silva Correia, K. Soldau, U. Christen, P. S. Tobias, and R. J. Ulevitch Lipopolysaccharide Is in Close Proximity to Each of the Proteins in Its Membrane Receptor Complex. TRANSFER FROM CD14 TO TLR4 AND MD-2 J. Biol. Chem., June 8, 2001; 276(24): 21129 - 21135. [Abstract] [Full Text] [PDF]
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A. Ozinsky, D. M. Underhill, J. D. Fontenot, A. M. Hajjar, K. D. Smith, C. B. Wilson, L. Schroeder, and A. Aderem The repertoire for pattern recognition of pathogens by the innate immune system is defined by cooperation between Toll-like receptors PNAS, December 5, 2000; 97(25): 13766 - 13771. [Abstract] [Full Text] [PDF]
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S. Sasu, D. LaVerda, N. Qureshi, D. T. Golenbock, and D. Beasley Chlamydia pneumoniae and Chlamydial Heat Shock Protein 60 Stimulate Proliferation of Human Vascular Smooth Muscle Cells via Toll-Like Receptor 4 and p44/p42 Mitogen-Activated Protein Kinase Activation Circ. Res., August 3, 2001; 89(3): 244 - 250. [Abstract] [Full Text] [PDF]
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