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CUTTING EDGE |


*
Maxwell Finland Laboratory for Infectious Diseases, Boston University School of Medicine, Boston Medical Center, Boston, MA 02118;
Department of Infectious Diseases, St. Jude Childrens Research Hospital, Memphis, TN 38105; and
Department of Microbiology and Immunology, Northwest Center for Medical Education, Indiana University School of Medicine, Gary, IN 46408
| Abstract |
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B.
CD14 coexpression synergistically enhanced TLR2-mediated activation. To
determine which components of Gram-positive cell walls activate Toll
proteins, we tested a soluble preparation of peptidoglycan
prepared from S. aureus. Soluble peptidoglycan
substituted for whole organisms. These data suggest that the similarity
of clinical response to invasive infection by Gram-positive and
Gram-negative bacteria is due to bacterial recognition via similar
TLRs. | Introduction |
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The outermost leaflet of the outer membrane of the Gram-negative bacterial cell wall consists of LPS, a toxic moiety that appears to be the cause of immune activation. Gram-positive bacteria, in contrast, do not contain a single constituent that is as clearly linked to the sepsis syndrome. Nevertheless, the interest in how Gram-positive bacteria activate the immune system is intense, fueled in large part by the enormous clinical significance of Gram-positive infections. The pneumococcus, for example, is a leading cause of death with a mortality rate in otherwise healthy elderly individuals of 40% (3). Staphylococcal infection is the major cause of bacteremia in US hospitals today (4). Together, these two species of bacteria account for nearly 75% of all antibiotic usage in the United States.
Although the exact mechanism of immune activation by Gram-positive bacteria remains unknown, recent studies of immune activation by bacterial LPS provide a clue. The family of Toll proteins appears to be responsible for specific immune recognition in Drosophila melanogaster. For example, the Toll homologue known as 18-wheeler is responsible for responses to Gram-negative bacteria (5), whereas Toll regulates antifungal responses (6). Yang et al. (7), and Kirschning et al. (8) recently demonstrated that a human homologue of Toll, known as Toll-like receptor 2 (TLR2),3 apparently functions as an LPS signal transducer when transfected into LPS nonresponder cell lines. This activity of TLR2 was potentiated by CD14, the LPS-binding receptor. Additional evidence that TLRs function as LPS signal transducers comes from positional cloning of Lps, the genetic locus for LPS sensitivity that is abnormal in C3H/HeJ mice. Lps mapped to the same region as TLR4 (9, 10). TLR4 cloned from the C3H/HeJ mouse proved to harbor a point mutation that rendered it nonfunctional (9, 10, 11), consistent with the concept the mutant TLR4 might function as a dominant-negative mutation accounting for LPS hyporesponsiveness in the C3H/HeJ mouse. Indeed, the LPS hyporesponder phenotype of C3H/HeJ mice is so profound that, despite the LPS signaling capability of TLR2, it seems likely that TLR4 is the major mammalian LPS signal transducer. This suggests the hypothesis that the true role of TLR2 is the recognition of other bacterial ligands that in some way are similar to LPS.
Like Gram-negative bacteria, major components of the Gram-positive bacterial cell wall employ CD14 for immune recognition. Both peptidoglycan (PGN) and lipoteichoic acid have been demonstrated to activate macrophages in a CD14-dependent manner (12, 13). Given the similarity in responses to exposure to Gram-positive bacteria and Gram-negative bacteria, and the common dependence on many of their cell wall products upon CD14, we hypothesized that the downstream elements of the signal transduction system might consist of common genetic elements. We report here that the coexpression of CD14 and human TLR2 resulted in the recognition of two distinct and clinically important genuses of Gram-positive bacteria. In contrast, TLR4 appears to be excluded as a component of a receptor system involved in the recognition of these types of bacteria. Furthermore, the recognition of these bacteria, at least in part, occurs via the PGN skeleton. The use of common receptor systems suggests that the often observed clinical parallels between Gram-positive and Gram-negative bacterial infection result from the activation of similar signal transduction systems.
| Materials and Methods |
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PBS,
-MEM, and Hams F-12 were obtained from
BioWhittaker (Walkersville, MD). Heat-inactivated FBS (LPS < 10
pg/ml) was obtained from Summit Biotechnology (Fort Collins, CO).
Ciprofloxacin was a gift from Miles Pharmaceuticals (West Haven, CT).
G418 was obtained from Life Technologies (Gaithersburg, MD). Hygromycin
B was obtained from Calbiochem (San Diego, CA). Anti-CD25 mAb
conjugated with FITC was obtained from Becton Dickinson (Bedford, MA).
Recombinant human IL-1ß was purchased from Genzyme (Cambridge, MA).
The soluble PGN (sPGN) released by Staphylococcus aureus Rb
in the presence of penicillin was purified as described previously
(14), prepared at 2 mg/ml in PBS, and stored at -20°C.
Before use, the suspensions were thawed and sonicated in an 80-W
sonicator bath (Lab Supply, Hicksville, NY) for 1 min. All other
reagents were obtained from Sigma (St. Louis, MO).
Cell lines
All cell lines were grown as adherent monolayers at 37°C in a
5% saturated CO2 atmosphere, and were passaged
at least twice weekly to maintain logarithmic growth. The engineering
of the CD14-expressing Chinese hamster ovary (CHO)-K1 reporter
fibroblast cell line CHO/CD14.elam.tac, also known as clone 3E10, has
been previously described in detail (15). This clonal line
has been cotransfected with CD14 and a NF-
B-dependent reporter
plasmid that drives the expression of surface CD25 Ag resulting from
LPS-, TNF
-, or IL-1ß-induced NF-
B translocation. The cDNAs for
human TLRs 2 and 4 were the gifts of Carsten Kirschning and Mike Rothe
(Tularik, South San Francisco, CA), and were cloned into the vector
pFLAG as described (8). Stable expression of TLRs was
obtained by cotransfection of these epitope-tagged plasmids with pcDNA3
(Invitrogen, San Diego, CA) or pRL/RSV/puro (gift of R. Kitchens,
University of Texas Southwestern Medical Center, Dallas, TX) into
CHO-K1 wild-type cells or CHO/CD14 reporter cells (16).
After selection in G418 (1 mg/ml) or puromycin (50 µg/ml), clonal
cell lines expressing high levels of human TLR2 or TLR4 were derived
using fluorescent-activated cell sorting combined with limiting
dilution cloning. In addition, CHO-K1 or 3E10 (CHO/CD14.elam.tac)
reporter cells were transfected with pcDNA3 as a control.
Bacterial strains, growth, and preparation
S. aureus (ATCC 25923) was grown in LPS-free
-MEM.
Streptococcus pneumoniae (D39) and its pneumolysin-defective
derivative (17) were grown in Brain Heart Infusion Broth
(Remel, Lenexa, KS) supplemented with horse blood (3.3%, Remel) and
ß-diphosphopyridine nucleotide (2 µg/ml) (Andersons broth). The
cells were grown to mid-logarythmic phase (OD620
= 0.4) and washed twice with PBS (BioWhittaker). The determination of
cell density was made by limiting dilution of washed bacteria. Bacteria
were resuspended in PBS, killed by incubation at 95°C for 20 min, and
stored at -20°C until use.
Flow cytometry analysis of CHO transfectants
Adherent monolayers of CHO cells were plated in 12-well tissue culture dishes at a density of 2.5 x 105 cells per well. After overnight incubation, the cells were stimulated for 18 h with various ligands. Cells were detached from the surface with trypsin/EDTA and assessed by flow microfluorometry for the presence of surface CD25 exactly as described (15).
Analysis of NF-
B translocation
Cells were plated in six-well tissue culture dishes at a density of 5 x 105 per well. After overnight incubation at 37°C in 5% CO2, the cells were stimulated for 45 min. Cells were washed in PBS, and nuclear extracts were prepared and analyzed using the EMSA exactly as described (18).
| Results and Discussion |
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B, a transcription
factor that is involved in cytokine regulation. No nuclear
translocation of NF-
B was observed in either CHO/Neo or CHO/CD14. In
contrast, CHO/TLR2 cells were activated with heat-killed S.
aureus at the highest concentration tested (Fig. 2
|
B reporter
construct in any of the CHO/CD14/TLR4 cells (e.g., Fig. 2
|
B
translocation (data not shown) and reporter cell transgene activation
as measured by surface CD25 expression (Fig. 3
To investigate which cell wall components of Gram-positive bacteria are
responsible for the activation of the transfectants, we exposed the
cells to purified sPGN from Staphylococcal cell walls. This cell wall
preparation was released from S. aureus Rb by penicillin
(average Mr = 125,000) and affinity
purified on a vancomycin column (14). Quantitative
analysis of the PGN demonstrated that
98.5% of the mass was
accounted for by amino acids and amino sugars. LPS content by
Limulus assay was
90 pg/mg. We observed the same pattern
of recognition of PGN as was observed with the whole organisms: while
CHO/CD14 cells had no response, expression of TLR2, but not TLR4,
rendered these cells responsive to PGN (Fig. 4
). Furthermore, we have observed strong
TLR2-dependent responses to a separately prepared PGN preparation (gift
of W. Fischer, Universitat Erlangen-Nurnberg, Erlangen, Germany) from a
strain of S. pneumoniae (25).
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The discovery that Drosophila Toll, a primitive receptor with IL-1-receptor homology (26), imparts some degree of pathogen specificity was a clue that similar molecules in mammals might account for the ability of the host to recognize and respond to so many dissimilar organisms. Like 18-wheeler in the fly, TLR4 may be more specific for Gram-negative bacteria and their LPS, whereas other TLRs might have other patterns of ligand recognition. There are currently at least four TLRs that have been identified in flies; given the relative complexity of the Drosophila genome compared with human, there might prove to be several dozen mammalian TLRs.
It is tempting to speculate that like the IL-1R (27), TLRs might form heterodimeric complexes upon ligand binding. The specificity for one bacterial product over another might then be best accounted for by which TLRs comprise the signaling receptor. With dozens of potentially available TLRs, the ability of immune cells to recognize a diverse array of stimuli would be very large. Coexpression of TLRs with more specific binding receptors such as CD14, might further define and expand the repertoire of the innate immune system.
Although the evidence that TLRs actually bind bacterial products remains to be convincingly elucidated, it seems likely that these receptors directly interact with their pathogenic targets. Despite our efforts, we were unable to observe the direct binding of bacteria to TLRs. Although there are numerous technical reasons why such an experiment might not produce a predicted result, other possibilities need to be explored. One prominent possibility is that Ag exposure results in the processing of an endogenous ligand that activates TLRs, much like the proteolytic peptide spatzle is thought to be the true ligand for Toll receptors in Drosophila (28). Whatever the picture that ultimately emerges for how TLRs function to provide specificity of recognition for diverse types of bacteria, the use of a common family of signaling receptors by seemingly diverse bacteria may explain why the clinical picture of sepsis caused by Gram-negative bacteria and Gram-positive bacteria is nearly identical.
| Acknowledgments |
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| Footnotes |
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2 Address correspondence and reprint requests to Dr. Douglas Golenbock, Maxwell Finland Laboratory for Infectious Diseases, 774 Albany Street, Boston, MA 02118. E-mail address: ![]()
3 Abbreviations used in this paper: TLR, Toll-like receptor; PGN, peptidoglycan; sPGN, soluble PGN; CHO, Chinese hamster ovary fibroblasts. ![]()
Received for publication March 26, 1999. Accepted for publication April 26, 1999.
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G. Elson, I. Dunn-Siegrist, B. Daubeuf, and J. Pugin Contribution of Toll-like receptors to the innate immune response to Gram-negative and Gram-positive bacteria Blood, February 15, 2007; 109(4): 1574 - 1583. [Abstract] [Full Text] [PDF] |
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M. A. Wolfert, A. Roychowdhury, and G.-J. Boons Modification of the Structure of Peptidoglycan Is a Strategy To Avoid Detection by Nucleotide-Binding Oligomerization Domain Protein 1 Infect. Immun., February 1, 2007; 75(2): 706 - 713. [Abstract] [Full Text] [PDF] |
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L. J. Quinton, M. R. Jones, B. T. Simms, M. S. Kogan, B. E. Robson, S. J. Skerrett, and J. P. Mizgerd Functions and Regulation of NF-{kappa}B RelA during Pneumococcal Pneumonia J. Immunol., February 1, 2007; 178(3): 1896 - 1903. [Abstract] [Full Text] [PDF] |
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A. Srivastava, H. Casey, N. Johnson, O. Levy, and R. Malley Recombinant Bactericidal/Permeability-Increasing Protein rBPI21 Protects against Pneumococcal Disease Infect. Immun., January 1, 2007; 75(1): 342 - 349. [Abstract] [Full Text] [PDF] |
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H. S. Hardarson, J. S. Baker, Z. Yang, E. Purevjav, C.-H. Huang, L. Alexopoulou, N. Li, R. A. Flavell, N. E. Bowles, and J. G. Vallejo Toll-like receptor 3 is an essential component of the innate stress response in virus-induced cardiac injury Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H251 - H258. [Abstract] [Full Text] [PDF] |
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K. K. B. Gorden, X. Qiu, J. J. L. Battiste, P. P. D. Wightman, J. P. Vasilakos, and S. S. Alkan Oligodeoxynucleotides Differentially Modulate Activation of TLR7 and TLR8 by Imidazoquinolines J. Immunol., December 1, 2006; 177(11): 8164 - 8170. [Abstract] [Full Text] [PDF] |
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K. W. Boehme, M. Guerrero, and T. Compton Human Cytomegalovirus Envelope Glycoproteins B and H Are Necessary for TLR2 Activation in Permissive Cells J. Immunol., November 15, 2006; 177(10): 7094 - 7102. [Abstract] [Full Text] [PDF] |
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P. S. Patole, R. D. Pawar, M. Lech, D. Zecher, H. Schmidt, S. Segerer, A. Ellwart, A. Henger, M. Kretzler, and H.-J. Anders Expression and regulation of Toll-like receptors in lupus-like immune complex glomerulonephritis of MRL-Fas(lpr) mice Nephrol. Dial. Transplant., November 1, 2006; 21(11): 3062 - 3073. [Abstract] [Full Text] [PDF] |
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J.E. den Hartog, S.A. Morre, and J.A. Land Chlamydia trachomatis-associated tubal factor subfertility: immunogenetic aspects and serological screening Hum. Reprod. Update, November 1, 2006; 12(6): 719 - 730. [Abstract] [Full Text] [PDF] |
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M. Triantafilou, F. G. J. Gamper, R. M. Haston, M. A. Mouratis, S. Morath, T. Hartung, and K. Triantafilou Membrane Sorting of Toll-like Receptor (TLR)-2/6 and TLR2/1 Heterodimers at the Cell Surface Determines Heterotypic Associations with CD36 and Intracellular Targeting J. Biol. Chem., October 13, 2006; 281(41): 31002 - 31011. [Abstract] [Full Text] [PDF] |
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S. Santos-Sierra, D. T. Golenbock, and P. Henneke Toll-like receptor-dependent discrimination of streptococci Innate Immunity, October 1, 2006; 12(5): 307 - 312. [Abstract] [PDF] |
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J. M. Buckley, J. H. Wang, and H. P. Redmond Cellular reprogramming by gram-positive bacterial components: a review J. Leukoc. Biol., October 1, 2006; 80(4): 731 - 741. [Abstract] [Full Text] [PDF] |
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J. Bubeck Wardenburg, W. A. Williams, and D. Missiakas Host defenses against Staphylococcus aureus infection require recognition of bacterial lipoproteins PNAS, September 12, 2006; 103(37): 13831 - 13836. [Abstract] [Full Text] [PDF] |
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U. Malipiero, U. Koedel, H.-W. Pfister, P. Leveen, K. Burki, W. Reith, and A. Fontana TGF{beta} receptor II gene deletion in leucocytes prevents cerebral vasculitis in bacterial meningitis Brain, September 1, 2006; 129(9): 2404 - 2415. [Abstract] [Full Text] [PDF] |
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I. Herrmann, M. Kellert, H. Schmidt, A. Mildner, U. K. Hanisch, W. Bruck, M. Prinz, and R. Nau Streptococcus pneumoniae Infection Aggravates Experimental Autoimmune Encephalomyelitis via Toll-Like Receptor 2. Infect. Immun., August 1, 2006; 74(8): 4841 - 4848. [Abstract] [Full Text] [PDF] |
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T. H. Mogensen, S. R. Paludan, M. Kilian, and L. Ostergaard Live Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis activate the inflammatory response through Toll-like receptors 2, 4, and 9 in species-specific patterns J. Leukoc. Biol., August 1, 2006; 80(2): 267 - 277. [Abstract] [Full Text] [PDF] |
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T. Sashihara, N. Sueki, and S. Ikegami An analysis of the effectiveness of heat-killed lactic acid bacteria in alleviating allergic diseases. J Dairy Sci, August 1, 2006; 89(8): 2846 - 2855. [Abstract] [Full Text] [PDF] |
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D. M. Jawdat, G. Rowden, and J. S. Marshall Mast Cells Have a Pivotal Role in TNF-Independent Lymph Node Hypertrophy and the Mobilization of Langerhans Cells in Response to Bacterial Peptidoglycan J. Immunol., August 1, 2006; 177(3): 1755 - 1762. [Abstract] [Full Text] [PDF] |
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L. I. Pahlman, M. Morgelin, J. Eckert, L. Johansson, W. Russell, K. Riesbeck, O. Soehnlein, L. Lindbom, A. Norrby-Teglund, R. R. Schumann, et al. Streptococcal M Protein: A Multipotent and Powerful Inducer of Inflammation J. Immunol., July 15, 2006; 177(2): 1221 - 1228. [Abstract] [Full Text] [PDF] |
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J. A. McCullers Insights into the Interaction between Influenza Virus and Pneumococcus Clin. Microbiol. Rev., July 1, 2006; 19(3): 571 - 582. [Abstract] [Full Text] [PDF] |
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S. Lehnardt, P. Henneke, E. Lien, D. L. Kasper, J. J. Volpe, I. Bechmann, R. Nitsch, J. R. Weber, D. T. Golenbock, and T. Vartanian A Mechanism for Neurodegeneration Induced by Group B Streptococci through Activation of the TLR2/MyD88 Pathway in Microglia J. Immunol., July 1, 2006; 177(1): 583 - 592. [Abstract] [Full Text] [PDF] |
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C. Mold and T. W. Du Clos C-Reactive Protein Increases Cytokine Responses to Streptococcus pneumoniae through Interactions with Fc{gamma} Receptors. J. Immunol., June 15, 2006; 176(12): 7598 - 7604. [Abstract] [Full Text] [PDF] |
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P. Henneke and R. Berner Interaction of neonatal phagocytes with group B streptococcus: recognition and response. Infect. Immun., June 1, 2006; 74(6): 3085 - 3095. [Full Text] [PDF] |
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L. E. Cole, K. L. Elkins, S. M. Michalek, N. Qureshi, L. J. Eaton, P. Rallabhandi, N. Cuesta, and S. N. Vogel Immunologic Consequences of Francisella tularensis Live Vaccine Strain Infection: Role of the Innate Immune Response in Infection and Immunity. J. Immunol., June 1, 2006; 176(11): 6888 - 6899. [Abstract] [Full Text] [PDF] |
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H. Fang, L. Xu, T. Y. Chen, J. M. Cyr, and D. M. Frucht Anthrax Lethal Toxin Has Direct and Potent Inhibitory Effects on B Cell Proliferation and Immunoglobulin Production J. Immunol., May 15, 2006; 176(10): 6155 - 6161. [Abstract] [Full Text] [PDF] |
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C. A. Lindemans, P. J. Coffer, I. M. M. Schellens, P. M. A. de Graaff, J. L. L. Kimpen, and L. Koenderman Respiratory Syncytial Virus Inhibits Granulocyte Apoptosis through a Phosphatidylinositol 3-Kinase and NF-{kappa}B-Dependent Mechanism J. Immunol., May 1, 2006; 176(9): 5529 - 5537. [Abstract] [Full Text] [PDF] |
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D. L. Hasty, S. Meron-Sudai, K. H. Cox, T. Nagorna, E. Ruiz-Bustos, E. Losi, H. S. Courtney, E. A. Mahrous, R. Lee, and I. Ofek Monocyte and Macrophage Activation by Lipoteichoic Acid Is Independent of Alanine and Is Potentiated by Hemoglobin J. Immunol., May 1, 2006; 176(9): 5567 - 5576. [Abstract] [Full Text] [PDF] |
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U. Buwitt-Beckmann, H. Heine, K.-H. Wiesmuller, G. Jung, R. Brock, S. Akira, and A. J. Ulmer TLR1- and TLR6-independent Recognition of Bacterial Lipopeptides J. Biol. Chem., April 7, 2006; 281(14): 9049 - 9057. [Abstract] [Full Text] [PDF] |
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S. Traub, S. von Aulock, T. Hartung, and C. Hermann Invited review: MDP and other muropeptides direct and synergistic effects on the immune system Innate Immunity, April 1, 2006; 12(2): 69 - 85. [Abstract] [PDF] |
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F.-S. X. Yu and L. D. Hazlett Toll-like Receptors and the Eye. Invest. Ophthalmol. Vis. Sci., April 1, 2006; 47(4): 1255 - 1263. [Full Text] [PDF] |
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B. Schmeck, S. Huber, K. Moog, J. Zahlten, A. C. Hocke, B. Opitz, S. Hammerschmidt, T. J. Mitchell, M. Kracht, S. Rosseau, et al. Pneumococci induced TLR- and Rac1-dependent NF-{kappa}B-recruitment to the IL-8 promoter in lung epithelial cells Am J Physiol Lung Cell Mol Physiol, April 1, 2006; 290(4): L730 - L737. [Abstract] [Full Text] [PDF] |
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E. LeBouder, J. E. Rey-Nores, A.-C. Raby, M. Affolter, K. Vidal, C. A. Thornton, and M. O. Labeta Modulation of Neonatal Microbial Recognition: TLR-Mediated Innate Immune Responses Are Specifically and Differentially Modulated by Human Milk J. Immunol., March 15, 2006; 176(6): 3742 - 3752. [Abstract] [Full Text] [PDF] |
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G. K. Paterson and T. J. Mitchell Innate immunity and the pneumococcus Microbiology, February 1, 2006; 152(2): 285 - 293. [Abstract] [Full Text] [PDF] |
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H. Tada, S. Aiba, K.-I. Shibata, T. Ohteki, and H. Takada Synergistic Effect of Nod1 and Nod2 Agonists with Toll-Like Receptor Agonists on Human Dendritic Cells To Generate Interleukin-12 and T Helper Type 1 Cells Infect. Immun., December 1, 2005; 73(12): 7967 - 7976. [Abstract] [Full Text] [PDF] |
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H. Wang, D. Gupta, X. Li, and R. Dziarski Peptidoglycan Recognition Protein 2 (N-Acetylmuramoyl-L-Ala Amidase) Is Induced in Keratinocytes by Bacteria through the p38 Kinase Pathway Infect. Immun., November 1, 2005; 73(11): 7216 - 7225. [Abstract] [Full Text] [PDF] |
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T. Kielian, A. Haney, P. M. Mayes, S. Garg, and N. Esen Toll-Like Receptor 2 Modulates the Proinflammatory Milieu in Staphylococcus aureus-Induced Brain Abscess Infect. Immun., November 1, 2005; 73(11): 7428 - 7435. [Abstract] [Full Text] [PDF] |
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J. S. Hadley, J. E. Wang, S. J. Foster, C. Thiemermann, and C. J. Hinds Peptidoglycan of Staphylococcus aureus Upregulates Monocyte Expression of CD14, Toll-Like Receptor 2 (TLR2), and TLR4 in Human Blood: Possible Implications for Priming of Lipopolysaccharide Signaling Infect. Immun., November 1, 2005; 73(11): 7613 - 7619. [Abstract] [Full Text] [PDF] |
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A. M. C. van Rossum, E. S. Lysenko, and J. N. Weiser Host and Bacterial Factors Contributing to the Clearance of Colonization by Streptococcus pneumoniae in a Murine Model Infect. Immun., November 1, 2005; 73(11): 7718 - 7726. [Abstract] [Full Text] [PDF] |
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T. Luxameechanporn, V. Kirtsreesakul, J. Klemens, P. Khoury, K. Thompson, and R. M. Naclerio Evaluation of Importance of Toll-like Receptor 4 in Acute Streptococcus pneumoniae Sinusitis in Mice Arch Otolaryngol Head Neck Surg, November 1, 2005; 131(11): 1001 - 1006. [Abstract] [Full Text] [PDF] |
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A. Srivastava, P. Henneke, A. Visintin, S. C. Morse, V. Martin, C. Watkins, J. C. Paton, M. R. Wessels, D. T. Golenbock, and R. Malley The Apoptotic Response to Pneumolysin Is Toll-Like Receptor 4 Dependent and Protects against Pneumococcal Disease Infect. Immun., October 1, 2005; 73(10): 6479 - 6487. [Abstract] [Full Text] [PDF] |
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R. Dziarski and D. Gupta Peptidoglycan recognition in innate immunity Innate Immunity, October 1, 2005; 11(5): 304 - 310. [Abstract] [PDF] |
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H. Echchannaoui, K. Frei, M. Letiembre, R. M. Strieter, Y. Adachi, and R. Landmann CD14 deficiency leads to increased MIP-2 production, CXCR2 expression, neutrophil transmigration, and early death in pneumococcal infection J. Leukoc. Biol., September 1, 2005; 78(3): 705 - 715. [Abstract] [Full Text] [PDF] |
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K. D. Salazar, P. de la Rosa, J. B. Barnett, and R. Schafer The Polysaccharide Antibody Response after Streptococcus pneumoniae Vaccination Is Differentially Enhanced or Suppressed by 3,4-Dichloropropionanilide and 2,4-Dichlorophenoxyacetic Acid Toxicol. Sci., September 1, 2005; 87(1): 123 - 133. [Abstract] [Full Text] [PDF] |
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P. Brun, I. Castagliuolo, M. Pinzani, G. Palu, and D. Martines Exposure to bacterial cell wall products triggers an inflammatory phenotype in hepatic stellate cells Am J Physiol Gastrointest Liver Physiol, September 1, 2005; 289(3): G571 - G578. [Abstract] [Full Text] [PDF] |
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R. P Miech Pathophysiology of Mifepristone-Induced Septic Shock Due to Clostridium sordellii Ann. Pharmacother., September 1, 2005; 39(9): 1483 - 1488. [Abstract] [Full Text] [PDF] |
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R. Dziarski and D. Gupta Staphylococcus aureus Peptidoglycan Is a Toll-Like Receptor 2 Activator: a Reevaluation Infect. Immun., August 1, 2005; 73(8): 5212 - 5216. [Abstract] [Full Text] [PDF] |
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C. Roura-Mir, L. Wang, T.-Y. Cheng, I. Matsunaga, C. C. Dascher, S. L. Peng, M. J. Fenton, C. Kirschning, and D. B. Moody Mycobacterium tuberculosis Regulates CD1 Antigen Presentation Pathways through TLR-2 J. Immunol., August 1, 2005; 175(3): 1758 - 1766. [Abstract] [Full Text] [PDF] |
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H. Fan, B. Zingarelli, O. M. Peck, G. Teti, G. E. Tempel, P. V. Halushka, and J. A. Cook Lipopolysaccharide- and gram-positive bacteria-induced cellular inflammatory responses: role of heterotrimeric G{alpha}i proteins Am J Physiol Cell Physiol, August 1, 2005; 289(2): C293 - C301. [Abstract] [Full Text] [PDF] |
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B. Fournier and D. J. Philpott Recognition of Staphylococcus aureus by the Innate Immune System Clin. Microbiol. Rev., July 1, 2005; 18(3): 521 - 540. [Abstract] [Full Text] [PDF] |
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