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Cutting Edge |


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Epithelial Pathobiology Division, Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322; and
Department of Molecular Biology, Genentech, Inc., South San Francisco, CA 94080
| Abstract |
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B gene expression in response to
flagellin. The response depended on both extracellular leucine-rich
repeats and intracellular Toll/IL-1R homology region of TLR5 as well as
the adaptor protein MyD88. Furthermore, immunolocalization and cell
surface-selective biotinylation revealed that TLR5 is expressed
exclusively on the basolateral surface of intestinal epithelia, thus
providing a molecular basis for the polarity of this innate immune
response. Thus, detection of flagellin by basolateral TLR5 mediates
epithelial-driven inflammatory responses to
Salmonella. | Introduction |
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Toll-like receptors
(TLR)4 are an
evolutionarily conserved family of receptors that function in innate
immunity via recognition of conserved patterns in bacterial molecules
(for review, see Ref. 7). Given that the ligands for the
majority of cloned TLRs have yet to be identified, we explored the
possibility that a TLR would be a good candidate to mediate
inflammatory responses to flagellin. Indeed, Hayashi et al.
(8) recently screened bacterial products for ability to
activate TLR5 and found that flagellin could activate NF-
B-mediated
gene expression in TLR5-transfected cells. We report here that this
function is specific to TLR5 in that of all known TLRs
(1, 2, 3, 4, 5, 6, 7, 8, 9, 10), only TLR5 could activate proinflammatory gene
expression in response to flagellin. Further, TLR5 is expressed on the
basolateral, but not apical, surface of model epithelia, thus providing
a mechanism by which microbes that invade or translocate flagellin, but
not commensal bacteria, induce intestinal epithelia to orchestrate an
inflammatory response.
| Materials and Methods |
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Model human intestinal epithelia were prepared by culturing the
colonic cell line T84 on collagen-coated permeable supports as
previously described (9). Model epithelia were used 614
days after plating and after verification that they had achieved a
transepithelial electrical resistance of at least 1000
·cm2, thus indicating a high degree of
surface polarity. COS-7, 293, and HeLa cell lines were cultured
in DMEM with 10% FBS, 2 µM L-glutamine, 100 U/ml
penicillin, and 100 µg/ml streptomycin. Transient transfections were
conducted using Superfect (Qiagen, Chatsworth, CA) for COS and 293
cells and Effectene (Qiagen) for HeLa cells, according to the
manufacturers instructions. MG-262 was obtained from Affiniti
(Exeter, U.K.). Purified flagellin was prepared as previously described
(3).
Construction of TLR expression plasmids
Full length human TLR cDNAs (TLRs 110) were cloned from a
human fetal lung library into the pRKN. N-terminal epitope tag versions
(gD.TLR) linking TLRs to the first 53 aa of HSV-1 glycoprotein D (gD)
were constructed as previously described (10). The
predicted amino acid sequence for TLR5 matched that previously
published (11) except for the following substitutions:
V233L, C352L and L616F. TLR5 deletion plasmids were constructed as
follows: gD.TLR5 in pRKN were restricted with XhoI (deletion
of aa (
) 1191), EcoRV and MfeI
(
408591), and BsrGI (
695858). The resulting cDNAs
were gel purified and religated. Protein expression was confirmed by
immunoprecipitation and immunoblotting using gD mAb (Genentech, South
San Francisco, CA).
Luciferase reporter and other proinflammatory assays
293, COS, or HeLa cells were plated (in 12-well plates; 1
x 105 cells/well) and transfected 18 h
later with expression plasmids and 0.5 µg luciferase reporter plasmid
pGL3-ELAM.tk and 0.1 µg Renilla luciferase reporter vector
as an internal control. After 24 h, cells were treated with
flagellin (100 ng/ml) or TNF-
(60 ng/ml) for 6 h, and
luciferase was assayed via the Dual-Luciferase system (Promega,
Madison, WI). Data are expressed as relative luciferase activity
representing the mean ± SE of duplicate experiments and were
obtained by calculating the ratio of firefly luciferase activity and
Renilla luciferase activity. IL-8 secretion, I
B
degradation, and I
B
phosphorylation were measured as previously
described (12).
Fluorescence microscopy and FACS analysis
Confocal microscopy was performed on paraformaldehyde model
epithelia as previously described (13). FACS analysis was
performed on confluent T84 cells, disassociated with EGTA as previously
described (13) using a goat polyclonal Ab to the
N-terminal region of TLR5 and competing immunogen peptide from Santa
Cruz Biotechnology (Santa Cruz, CA). Isolation of apically or
basolaterally biotinylated proteins was performed as previously
described (14). Western blotting of such lysates was
performed with a 1/800 dilution of TLR5 rabbit polyclonal Ab directed
at aa 154280 purchased from Santa Cruz Biotechnology. Abs to
E-cadherin and IFN-
-inducible protein 82 were a gift from C. Parkos
(Emory University, Atlanta, GA).
| Results |
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B activation with the proteasome inhibitor MG-262
(15) blocked this IL-8 secretion by
80% (data not
shown). Further, basolateral flagellin induced NF-
B nuclear
translocation (Fig. 1
B
(Fig. 1
,
confirming that flagellin induces epithelial chemokine expression via
the activation of NF-
B.
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B activation is not specific to intestinal
epithelial cells. Rather, NF-
B-mediated responses also occur in
monocytic cells (16) as well as in such well-characterized
cell lines as COS cells and 293 cells (Fig. 2
B activation in
response to flagellin. We observed that transfection of 293 cells with
a dominant-negative TLR effector protein MyD88 (
152296) that
blocks most TLR responses (17, 18) also prevented NF-
B
activation in response to flagellin, but not TNF-
(negative
control), suggesting that a TLR was mediating NF-
B activation in
response to flagellin (Fig. 2
|
B in response to flagellin and found HeLa cells fit this
criteria (Fig. 2
B reporter gene in
response to flagellin was measured. HeLa cells transfected with TLR5
exhibited
10-fold activation of NF-
B-mediated gene expression,
whereas no activation was observed for HeLa transfected with any of the
other TLRs (Fig. 3
B
activation in TLR5-expressing HeLa was prevented by coexpressing
dominant-negative MyD88 (Fig. 3
695858), but not
from analogous mutants of TLR4 (Fig. 3
|
100 kDa (Fig. 5C) likely due to differential
glycosylation. As controls (not shown), we verified that
IFN-
-inducible protein 82 and E-cadherin were preferentially
expressed on the apical and basolateral surfaces, respectively, as
previously described (19, 20). Thus, the polarity of TLR5
expression matches the polarity of the response to flagellin, further
supporting the notion that flagellin activation of intestinal epithelia
is mediated by TLR5.
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| Discussion |
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B pathway, is an essential component of
innate immunity (21). TLRs play a key role in such innate
immune pathways via recognition of conserved microbial molecular
patterns, thus activating immune inflammatory responses. However,
because components of both pathogenic and commensal bacteria can
activate TLRs, host tissues that are normally densely colonized by
commensal bacteria must be able to distinguish commensal from
pathogenic organisms to avoid being in a constant state of
inflammation. For example, bacterial flagellins that are secreted by
both pathogenic and commensal bacteria have the potential to activate
epithelial chemokine secretion but can only do so upon translocation
from the luminal domain (where commensal strains are located) to the
basolateral membrane domain (3). Such translocation of
flagellin can be mediated by pathogens such as Salmonella
typhimurium, but not by commensal Escherichia coli
strains. This report identifies the molecular mechanism by which
intestinal epithelia distinguish between basolateral and apical
flagellin, namely, the basolateral expression of TLR5 that serves as
the flagellin receptor. In addition to its expression on colonic
epithelium, TLR5 is expressed in internal tissues including heart,
brain, spleen, kidney, and testis, suggesting a wide role for TLR5 in
host defense (11). Supporting this notion, mutations in
TLR5 result in an increased susceptibility of mice to
Salmonella infection (11). TLR5 expressed on the basolateral surface of intestinal epithelia ought to be able to detect the invasion of a large variety of microbes and is positioned to do so at a very early step in the invasive process. Importantly, this innate immune mechanism could be activated not only by invasive pathogens but also by commensal organisms that had somehow, perhaps opportunistically, breached the epithelium. Recruitment of inflammatory cells in response to TLR5-mediated chemokine secretion could thus prevent systemic penetration of such locally invading microbes, hence preventing the dire consequences that occur when pathogenic or commensal bacteria achieve systemic infection in humans. Interestingly, S. typhimurium may translocate flagellin independent of bacterial invasion (3) and thus may use TLR5 as a mechanism to induce intestinal inflammation and the associated diarrhea that aids in their dissemination to new hosts. Additionally, ligation of basolateral TLR5 by flagellin secreted from commensal organisms may occur in states of epithelial barrier dysfunction such as inflammatory bowel disease and thus may play a role in inducing or exacerbating the inflammation that characterizes these disorders.
| Acknowledgments |
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| Footnotes |
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2 Address correspondence and reprint requests to Dr. Andrew T. Gewirtz, Epithelial Pathobiology Division, Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322. E-mail address: agewirt{at}emory.edu; or Dr. Paul J. Godowski, Genentech Inc., South San Francisco, CA 94080. E-mail address: ski{at}gene.com ![]()
3 A.T.G. and T.A.N. contributed equally to this work. ![]()
4 Abbreviations used in this paper: TLR, Toll-like receptor; gD, glycoprotein D;
, deletion of amino acids. ![]()
Received for publication May 30, 2001.
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J. W. Du, F. Zhang, J. E. Capo-Aponte, S. D. Tachado, J. Zhang, F.-S. X. Yu, R. A. Sack, H. Koziel, and P. S. Reinach AsialoGM1-Mediated IL-8 Release by Human Corneal Epithelial Cells Requires Coexpression of TLR5 Invest. Ophthalmol. Vis. Sci., November 1, 2006; 47(11): 4810 - 4818. [Abstract] [Full Text] [PDF] |
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M. Vijay-Kumar, H. Wu, R. Jones, G. Grant, B. Babbin, T. P. King, D. Kelly, A. T. Gewirtz, and A. S. Neish Flagellin Suppresses Epithelial Apoptosis and Limits Disease during Enteric Infection Am. J. Pathol., November 1, 2006; 169(5): 1686 - 1700. [Abstract] [Full Text] [PDF] |
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J. Heidemann, W. Domschke, T. Kucharzik, and C. Maaser Intestinal microvascular endothelium and innate immunity in inflammatory bowel disease: a second line of defense? Infect. Immun., October 1, 2006; 74(10): 5425 - 5432. [Full Text] [PDF] |
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R. C. Alaniz, L. A. Cummings, M. A. Bergman, S. L. Rassoulian-Barrett, and B. T. Cookson Salmonella typhimurium Coordinately Regulates FliC Location and Reduces Dendritic Cell Activation and Antigen Presentation to CD4+ T cells J. Immunol., September 15, 2006; 177(6): 3983 - 3993. [Abstract] [Full Text] [PDF] |
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C. J. Sanders, Y. Yu, D. A. Moore III, I. R. Williams, and A. T. Gewirtz Humoral immune response to flagellin requires T cells and activation of innate immunity. J. Immunol., September 1, 2006; 177(5): 2810 - 2818. [Abstract] [Full Text] [PDF] |
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V. Feuillet, S. Medjane, I. Mondor, O. Demaria, P. P. Pagni, J. E. Galan, R. A. Flavell, and L. Alexopoulou Involvement of Toll-like receptor 5 in the recognition of flagellated bacteria PNAS, August 15, 2006; 103(33): 12487 - 12492. [Abstract] [Full Text] [PDF] |
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Y. Wakabayashi, M. Kobayashi, S. Akashi-Takamura, N. Tanimura, K. Konno, K. Takahashi, T. Ishii, T. Mizutani, H. Iba, T. Kouro, et al. A Protein Associated with Toll-Like Receptor 4 (PRAT4A) Regulates Cell Surface Expression of TLR4 J. Immunol., August 1, 2006; 177(3): 1772 - 1779. [Abstract] [Full Text] [PDF] |
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J. Chun and A. Prince Activation of Ca2+-Dependent Signaling by TLR2 J. Immunol., July 15, 2006; 177(2): 1330 - 1337. [Abstract] [Full Text] [PDF] |
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P. A. Johanesen and M. B. Dwinell Flagellin-Independent Regulation of Chemokine Host Defense in Campylobacter jejuni-Infected Intestinal Epithelium. Infect. Immun., June 1, 2006; 74(6): 3437 - 3447. [Abstract] [Full Text] [PDF] |
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L. Romics Jr, G. Szabo, J. C. Coffey, J. H. Wang, and H. P. Redmond The Emerging Role of Toll-Like Receptor Pathways in Surgical Diseases Arch Surg, June 1, 2006; 141(6): 595 - 601. [Abstract] [Full Text] [PDF] |
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N. McNamara, M. Gallup, A. Sucher, I. Maltseva, D. McKemy, and C. Basbaum AsialoGM1 and TLR5 Cooperate in Flagellin-Induced Nucleotide Signaling to Activate Erk1/2 Am. J. Respir. Cell Mol. Biol., June 1, 2006; 34(6): 653 - 660. [Abstract] [Full Text] [PDF] |
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A. T. Gewirtz, M. Vijay-Kumar, S. R. Brant, R. H. Duerr, D. L. Nicolae, and J. H. Cho Dominant-negative TLR5 polymorphism reduces adaptive immune response to flagellin and negatively associates with Crohn's disease Am J Physiol Gastrointest Liver Physiol, June 1, 2006; 290(6): G1157 - G1163. [Abstract] [Full Text] [PDF] |
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Y. Yu, S. Nagai, H. Wu, A. S. Neish, S. Koyasu, and A. T. Gewirtz TLR5-Mediated Phosphoinositide 3-Kinase Activation Negatively Regulates Flagellin-Induced Proinflammatory Gene Expression J. Immunol., May 15, 2006; 176(10): 6194 - 6201. [Abstract] [Full Text] [PDF] |
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A. Prince Flagellar Activation of Epithelial Signaling Am. J. Respir. Cell Mol. Biol., May 1, 2006; 34(5): 548 - 551. [Abstract] [Full Text] [PDF] |
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V. Lievin-Le Moal and A. L. Servin The Front Line of Enteric Host Defense against Unwelcome Intrusion of Harmful Microorganisms: Mucins, Antimicrobial Peptides, and Microbiota Clin. Microbiol. Rev., April 1, 2006; 19(2): 315 - 337. [Abstract] [Full Text] [PDF] |
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W. Lu, A. Hisatsune, T. Koga, K. Kato, I. Kuwahara, E. P. Lillehoj, W. Chen, A. S. Cross, S. J. Gendler, A. T. Gewirtz, et al. Cutting Edge: Enhanced Pulmonary Clearance of Pseudomonas aeruginosa by Muc1 Knockout Mice J. Immunol., April 1, 2006; 176(7): 3890 - 3894. [Abstract] [Full Text] [PDF] |
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S. Chabot, J. S. Wagner, S. Farrant, and M. R. Neutra TLRs Regulate the Gatekeeping Functions of the Intestinal Follicle-Associated Epithelium J. Immunol., April 1, 2006; 176(7): 4275 - 4283. [Abstract] [Full Text] [PDF] |
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R. Sharma, S. Tesfay, F. L. Tomson, R. P. Kanteti, V. K. Viswanathan, and G. Hecht Balance of bacterial pro- and anti-inflammatory mediators dictates net effect of enteropathogenic Escherichia coli on intestinal epithelial cells Am J Physiol Gastrointest Liver Physiol, April 1, 2006; 290(4): G685 - G694. [Abstract] [Full Text] [PDF] |
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J. Tseng, J. Do, J. H. Widdicombe, and T. E. Machen Innate immune responses of human tracheal epithelium to Pseudomonas aeruginosa flagellin, TNF-{alpha}, and IL-1beta Am J Physiol Cell Physiol, March 1, 2006; 290(3): C678 - C690. [Abstract] [Full Text] [PDF] |
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C Mueller and A J Macpherson Layers of mutualism with commensal bacteria protect us from intestinal inflammation Gut, February 1, 2006; 55(2): 276 - 284. [Full Text] [PDF] |
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M. Raffatellu, D. Chessa, R. P. Wilson, C. Tukel, M. Akcelik, and A. J. Baumler Capsule-Mediated Immune Evasion: a New Hypothesis Explaining Aspects of Typhoid Fever Pathogenesis Infect. Immun., January 1, 2006; 74(1): 19 - 27. [Full Text] [PDF] |
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C. F. Ortega-Cava, S. Ishihara, M. A. K. Rumi, M. M. Aziz, H. Kazumori, T. Yuki, Y. Mishima, I. Moriyama, C. Kadota, N. Oshima, et al. Epithelial Toll-Like Receptor 5 Is Constitutively Localized in the Mouse Cecum and Exhibits Distinctive Down-Regulation during Experimental Colitis Clin. Vaccine Immunol., January 1, 2006; 13(1): 132 - 138. [Abstract] [Full Text] [PDF] |
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H. Zeng, H. Wu, V. Sloane, R. Jones, Y. Yu, P. Lin, A. T. Gewirtz, and A. S. Neish Flagellin/TLR5 responses in epithelia reveal intertwined activation of inflammatory and apoptotic pathways Am J Physiol Gastrointest Liver Physiol, January 1, 2006; 290(1): G96 - G108. [Abstract] [Full Text] [PDF] |
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A. Verma, S. K. Arora, S. K. Kuravi, and R. Ramphal Roles of Specific Amino Acids in the N Terminus of Pseudomonas aeruginosa Flagellin and of Flagellin Glycosylation in the Innate Immune Response Infect. Immun., December 1, 2005; 73(12): 8237 - 8246. [Abstract] [Full Text] [PDF] |
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X.-M. Chen, S. P. O'Hara, J. B. Nelson, P. L. Splinter, A. J. Small, P. S. Tietz, A. H. Limper, and N. F. LaRusso Multiple TLRs Are Expressed in Human Cholangiocytes and Mediate Host Epithelial Defense Responses to Cryptosporidium parvum via Activation of NF-{kappa}B J. Immunol., December 1, 2005; 175(11): 7447 - 7456. [Abstract] [Full Text] [PDF] |
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Z. Zhang, J.-P. Louboutin, D. J. Weiner, J. B. Goldberg, and J. M. Wilson Human Airway Epithelial Cells Sense Pseudomonas aeruginosa Infection via Recognition of Flagellin by Toll-Like Receptor 5 Infect. Immun., November 1, 2005; 73(11): 7151 - 7160. [Abstract] [Full Text] [PDF] |
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A. S. Ismail and L. V. Hooper Epithelial Cells and Their Neighbors. IV. Bacterial contributions to intestinal epithelial barrier integrity Am J Physiol Gastrointest Liver Physiol, November 1, 2005; 289(5): G779 - G784. [Abstract] [Full Text] [PDF] |
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R. W. DePaolo, R. Lathan, B. J. Rollins, and W. J. Karpus The Chemokine CCL2 Is Required for Control of Murine Gastric Salmonella enterica Infection Infect. Immun., October 1, 2005; 73(10): 6514 - 6522. [Abstract] [Full Text] [PDF] |
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O. Pino, M. Martin, and S. M. Michalek Cellular Mechanisms of the Adjuvant Activity of the Flagellin Component FljB of Salmonella enterica Serovar Typhimurium To Potentiate Mucosal and Systemic Responses Infect. Immun., October 1, 2005; 73(10): 6763 - 6770. [Abstract] [Full Text] [PDF] |
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H. Tsujimoto, T. Uchida, P. A. Efron, P. O. Scumpia, A. Verma, T. Matsumoto, S. K. Tschoeke, R. F. Ungaro, S. Ono, S. Seki, et al. Flagellin enhances NK cell proliferation and activation directly and through dendritic cell-NK cell interactions J. Leukoc. Biol., October 1, 2005; 78(4): 888 - 897. [Abstract] [Full Text] [PDF] |
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S. H. Rhee, E. Im, M. Riegler, E. Kokkotou, M. O'Brien, and C. Pothoulakis Pathophysiological role of Toll-like receptor 5 engagement by bacterial flagellin in colonic inflammation PNAS, September 20, 2005; 102(38): 13610 - 13615. [Abstract] [Full Text] [PDF] |
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S. E. Applequist, E. Rollman, M. D. Wareing, M. Liden, B. Rozell, J. Hinkula, and H.-G. Ljunggren Activation of Innate Immunity, Inflammation, and Potentiation of DNA Vaccination through Mammalian Expression of the TLR5 Agonist Flagellin J. Immunol., September 15, 2005; 175(6): 3882 - 3891. [Abstract] [Full Text] [PDF] |
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G. Caron, D. Duluc, I. Fremaux, P. Jeannin, C. David, H. Gascan, and Y. Delneste Direct Stimulation of Human T Cells via TLR5 and TLR7/8: Flagellin and R-848 Up-Regulate Proliferation and IFN-{gamma} Production by Memory CD4+ T Cells J. Immunol., August 1, 2005; 175(3): 1551 - 1557. [Abstract] [Full Text] [PDF] |
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E Cario BACTERIAL INTERACTIONS WITH CELLS OF THE INTESTINAL MUCOSA: TOLL-LIKE RECEPTORS AND NOD2 Gut, August 1, 2005; 54(8): 1182 - 1193. [Full Text] [PDF] |
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S. K. Arora, A. N. Neely, B. Blair, S. Lory, and R. Ramphal Role of Motility and Flagellin Glycosylation in the Pathogenesis of Pseudomonas aeruginosa Burn Wound Infections Infect. Immun., July 1, 2005; 73(7): 4395 - 4398. [Abstract] [Full Text] [PDF] |
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E. Andersen-Nissen, K. D. Smith, K. L. Strobe, S. L. R. Barrett, B. T. Cookson, S. M. Logan, and A. Aderem Evasion of Toll-like receptor 5 by flagellated bacteria PNAS, June 28, 2005; 102(26): 9247 - 9252. [Abstract] [Full Text] [PDF] |
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L. A. Cummings, S. L. R. Barrett, W. D. Wilkerson, I. Fellnerova, and B. T. Cookson FliC-Specific CD4+ T Cell Responses Are Restricted by Bacterial Regulation of Antigen Expression J. Immunol., June 15, 2005; 174(12): 7929 - 7938. [Abstract] [Full Text] [PDF] |
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B. J. Johnson, S. S. Dritz, K. A. Skjolaas-Wilson, T. E. Burkey, and J. E. Minton Interactive responses in gut immunity, and systemic and local changes in the insulin-like growth factor system in nursery pigs in response to Salmonella enterica serovar Typhimurium J Anim Sci, June 1, 2005; 83(13_suppl): E48 - 56. [Abstract] [Full Text] [PDF] |
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M. Vijay-Kumar, J. R. Gentsch, W. J. Kaiser, N. Borregaard, M. K. Offermann, A. S. Neish, and A. T. Gewirtz Protein Kinase R Mediates Intestinal Epithelial Gene Remodeling in Response to Double-Stranded RNA and Live Rotavirus J. Immunol., May 15, 2005; 174(10): 6322 - 6331. [Abstract] [Full Text] [PDF] |
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K. L. Mumy and B. A. McCormick Events at the Host-Microbial Interface of the Gastrointestinal Tract II. Role of the intestinal epithelium in pathogen-induced inflammation Am J Physiol Gastrointest Liver Physiol, May 1, 2005; 288(5): G854 - G859. [Abstract] [Full Text] [PDF] |
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M. T. Abreu, M. Fukata, and M. Arditi TLR Signaling in the Gut in Health and Disease J. Immunol., April 15, 2005; 174(8): 4453 - 4460. [Abstract] [Full Text] [PDF] |
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M. Iqbal, V. J. Philbin, G. S. K. Withanage, P. Wigley, R. K. Beal, M. J. Goodchild, P. Barrow, I. McConnell, D. J. Maskell, J. Young, et al. Identification and Functional Characterization of Chicken Toll-Like Receptor 5 Reveals a Fundamental Role in the Biology of Infection with Salmonella enterica Serovar Typhimurium Infect. Immun., April 1, 2005; 73(4): 2344 - 2350. [Abstract] [Full Text] [PDF] |
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M. W. Hornef and C. Bogdan The role of epithelial Toll-like receptor expression in host defense and microbial tolerance Innate Immunity, April 1, 2005; 11(2): 124 - 128. [Abstract] [PDF] |
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T. T. MacDonald and G. Monteleone Immunity, Inflammation, and Allergy in the Gut Science, March 25, 2005; 307(5717): 1920 - 1925. [Abstract] [Full Text] [PDF] |
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A. P. West, B. A. Dancho, and S. B. Mizel Gangliosides Inhibit Flagellin Signaling in the Absence of an Effect on Flagellin Binding to Toll-like Receptor 5 J. Biol. Chem., March 11, 2005; 280(10): 9482 - 9488. [Abstract] [Full Text] [PDF] |
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S. Totemeyer, P. Kaiser, D. J. Maskell, and C. E. Bryant Sublethal Infection of C57BL/6 Mice with Salmonella enterica Serovar Typhimurium Leads to an Increase in Levels of Toll-Like Receptor 1 (TLR1), TLR2, and TLR9 mRNA as Well as a Decrease in Levels of TLR6 mRNA in Infected Organs Infect. Immun., March 1, 2005; 73(3): 1873 - 1878. [Abstract] [Full Text] [PDF] |
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A. J. Ratner, E. S. Lysenko, M. N. Paul, and J. N. Weiser Synergistic proinflammatory responses induced by polymicrobial colonization of epithelial surfaces PNAS, March 1, 2005; 102(9): 3429 - 3434. [Abstract] [Full Text] [PDF] |
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S. V. Sitaraman, J.-M. Klapproth, D. A. Moore III, C. Landers, S. Targan, I. R. Williams, and A. T. Gewirtz Elevated flagellin-specific immunoglobulins in Crohn's disease Am J Physiol Gastrointest Liver Physiol, February 1, 2005; 288(2): G403 - G406. [Abstract] [Full Text] [PDF] |
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M. Raffatellu, R. P. Wilson, D. Chessa, H. Andrews-Polymenis, Q. T. Tran, S. Lawhon, S. Khare, L. G. Adams, and A. J. Baumler SipA, SopA, SopB, SopD, and SopE2 Contribute to Salmonella enterica Serotype Typhimurium Invasion of Epithelial Cells Infect. Immun., January 1, 2005; 73(1): 146 - 154. [Abstract] [Full Text] [PDF] |
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