Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

Science 291 (5508): 1544-1547

Copyright © 2001 by the American Association for the Advancement of Science

Induction of Direct Antimicrobial Activity Through Mammalian Toll-Like Receptors

Sybille Thoma-Uszynski,1* Steffen Stenger,2* Osamu Takeuchi,3 Maria Teresa Ochoa,1 Matthias Engele,2 Peter A. Sieling,1 Peter F. Barnes,4 Martin Röllinghoff,2 Pal L. Bölcskei,5 Manfred Wagner,5 Shizuo Akira,3 Michael V. Norgard,6 John T. Belisle,7 Paul J. Godowski,8 Barry R. Bloom,9 Robert L. Modlin1dagger

The mammalian innate immune system retains from Drosophila a family of homologous Toll-like receptors (TLRs) that mediate responses to microbial ligands. Here, we show that TLR2 activation leads to killing of intracellular Mycobacterium tuberculosis in both mouse and human macrophages, through distinct mechanisms. In mouse macrophages, bacterial lipoprotein activation of TLR2 leads to a nitric oxide-dependent killing of intracellular tubercle bacilli, but in human monocytes and alveolar macrophages, this pathway was nitric oxide-independent. Thus, mammalian TLRs respond (as Drosophila Toll receptors do) to microbial ligands and also have the ability to activate antimicrobial effector pathways at the site of infection.

1 Division of Dermatology, Department of Microbiology and Immunology and Molecular Biology Institute, UCLA School of Medicine, Los Angeles, CA 90095, USA.
2 Institute for Clinical Microbiology, Immunology and Hygiene, Universität Erlangen, 91054 Erlangen, Germany.
3 Department of Host Defense, Osaka University, Osaka, Japan.
4 Center for Pulmonary and Infectious Disease Control, Departments of Medicine, Cell Biology, and Immunology, University of Texas Health Center, Tyler, TX 75708-3154, USA.
5 Klinikum Nürnberg, Medical Clinic 3, 90419 Nürnberg, Germany.
6 University of Texas Southwestern Medical Center, Dallas, TX 75235, USA.
7 Department of Microbiology, Colorado State University, Fort Collins, CO 80523, USA.
8 Department of Molecular Biology, Genentech, South San Francisco, CA 94080, USA.
9 Office of the Dean, Harvard School of Public Health, Boston, MA 02115, USA.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: rmodlin{at}mednet.ucla.edu


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Key Role of Toll-Like Receptor 2 in the Inflammatory Response and Major Histocompatibility Complex Class II Downregulation in Brucella abortus-Infected Alveolar Macrophages.
M. C. Ferrero, M. S. Hielpos, N. B. Carvalho, P. Barrionuevo, P. P. Corsetti, G. H. Giambartolomei, S. C. Oliveira, P. C. Baldi, and A. Camilli (2014)
Infect. Immun. 82, 626-639
   Abstract »    Full Text »    PDF »
Polymorphisms within Toll-like receptors are associated with systemic lupus erythematosus in a cohort of Danish females.
M. J. Laska, A. Troldborg, B. Hansen, K. Stengaard-Pedersen, P. Junker, B. A. Nexo, and A. Voss (2014)
Rheumatology 53, 48-55
   Abstract »    Full Text »    PDF »
Genetic regulation of vesiculogenesis and immunomodulation in Mycobacterium tuberculosis.
P. Rath, C. Huang, T. Wang, T. Wang, H. Li, R. Prados-Rosales, O. Elemento, A. Casadevall, and C. F. Nathan (2013)
PNAS 110, E4790-E4797
   Abstract »    Full Text »    PDF »
TB or Not TB: That Is No Longer the Question.
R. L. Modlin and B. R. Bloom (2013)
Science Translational Medicine 5, 213sr6
   Full Text »    PDF »
Vitamin D status and TB treatment outcomes in adult patients in Tanzania: a cohort study.
S. Mehta, F. M. Mugusi, R. J. Bosch, S. Aboud, W. Urassa, E. Villamor, and W. W. Fawzi (2013)
BMJ Open 3, e003703
   Abstract »    Full Text »    PDF »
Species-specific PAMP recognition by TLR2 and evidence for species-restricted interaction with Dectin-1.
S. Willcocks, V. Offord, H.-M. Seyfert, T. J. Coffey, and D. Werling (2013)
J. Leukoc. Biol. 94, 449-458
   Abstract »    Full Text »    PDF »
Toll-Like Receptor 4-Linked Janus Kinase 2 Signaling Contributes to Internalization of Brucella abortus by Macrophages.
J. J. Lee, D. H. Kim, D. G. Kim, H. J. Lee, W. Min, M. H. Rhee, J. Y. Cho, M. Watarai, and S. Kim (2013)
Infect. Immun. 81, 2448-2458
   Abstract »    Full Text »    PDF »
Toll-like Receptor 1 N248S Single-Nucleotide Polymorphism Is Associated With Leprosy Risk and Regulates Immune Activation During Mycobacterial Infection.
C. de Sales Marques, V. N. Brito-de-Souza, L. T. A. Guerreiro, J. H. Martins, E. P. Amaral, C. C. Cardoso, I. M. F. Dias-Batista, W. L. da Silva, J. A. C. Nery, P. Medeiros, et al. (2013)
The Journal of Infectious Disease 208, 120-129
   Abstract »    Full Text »    PDF »
Innate Immunity and Its Regulation by Mast Cells.
A. L. St. John and S. N. Abraham (2013)
J. Immunol. 190, 4458-4463
   Abstract »    Full Text »    PDF »
Proteomic Profiling of Mycobacterium tuberculosis Identifies Nutrient-starvation-responsive Toxin-antitoxin Systems.
J. Albrethsen, J. Agner, S. R. Piersma, P. Hojrup, T. V. Pham, K. Weldingh, C. R. Jimenez, P. Andersen, and I. Rosenkrands (2013)
Mol. Cell. Proteomics 12, 1180-1191
   Abstract »    Full Text »    PDF »
Host Responses to Persistent Mycobacterium avium Subspecies paratuberculosis Infection in Surgically Isolated Bovine Ileal Segments.
C. Charavaryamath, P. Gonzalez-Cano, P. Fries, S. Gomis, K. Doig, E. Scruten, A. Potter, S. Napper, and P. J. Griebel (2013)
Clin. Vaccine Immunol. 20, 156-165
   Abstract »    Full Text »    PDF »
MprAB Regulates the espA Operon in Mycobacterium tuberculosis and Modulates ESX-1 Function and Host Cytokine Response.
X. Pang, B. Samten, G. Cao, X. Wang, A. R. Tvinnereim, X.-L. Chen, and S. T. Howard (2013)
J. Bacteriol. 195, 66-75
   Abstract »    Full Text »    PDF »
West Nile Virus: Biology, Transmission, and Human Infection.
T. M. Colpitts, M. J. Conway, R. R. Montgomery, and E. Fikrig (2012)
Clin. Microbiol. Rev. 25, 635-648
   Abstract »    Full Text »    PDF »
Human TOLLIP Regulates TLR2 and TLR4 Signaling and Its Polymorphisms Are Associated with Susceptibility to Tuberculosis.
J. A. Shah, J. C. Vary, T. T. H. Chau, N. D. Bang, N. T. B. Yen, J. J. Farrar, S. J. Dunstan, and T. R. Hawn (2012)
J. Immunol. 189, 1737-1746
   Abstract »    Full Text »    PDF »
Leishmania donovani Exploits Host Deubiquitinating Enzyme A20, a Negative Regulator of TLR Signaling, To Subvert Host Immune Response.
S. Srivastav, S. Kar, A. G. Chande, R. Mukhopadhyaya, and P. K. Das (2012)
J. Immunol. 189, 924-934
   Abstract »    Full Text »    PDF »
Nuclear Hormone Receptors Enable Macrophages and Dendritic Cells to Sense Their Lipid Environment and Shape Their Immune Response.
L. Nagy, A. Szanto, I. Szatmari, and L. Szeles (2012)
Physiol Rev 92, 739-789
   Abstract »    Full Text »    PDF »
Pig Bone Marrow-Derived Macrophages Resemble Human Macrophages in Their Response to Bacterial Lipopolysaccharide.
R. Kapetanovic, L. Fairbairn, D. Beraldi, D. P. Sester, A. L. Archibald, C. K. Tuggle, and D. A. Hume (2012)
J. Immunol. 188, 3382-3394
   Abstract »    Full Text »    PDF »
Suppression of the NF-{kappa}B Pathway by Diesel Exhaust Particles Impairs Human Antimycobacterial Immunity.
S. Sarkar, Y. Song, S. Sarkar, H. M. Kipen, R. J. Laumbach, J. Zhang, P. A. Ohman Strickland, C. R. Gardner, and S. Schwander (2012)
J. Immunol. 188, 2778-2793
   Abstract »    Full Text »    PDF »
TLR2 Signaling Depletes IRAK1 and Inhibits Induction of Type I IFN by TLR7/9.
Y. C. Liu, D. P. Simmons, X. Li, D. W. Abbott, W. H. Boom, and C. V. Harding (2012)
J. Immunol. 188, 1019-1026
   Abstract »    Full Text »    PDF »
Essential role of Toll-like receptor 2 in macrophage activation by glycogen.
R. Kakutani, Y. Adachi, H. Takata, T. Kuriki, and N. Ohno (2012)
Glycobiology 22, 146-159
   Abstract »    Full Text »    PDF »
Vitamin D Is Required for IFN-{gamma}-Mediated Antimicrobial Activity of Human Macrophages.
M. Fabri, S. Stenger, D.-M. Shin, J.-M. Yuk, P. T. Liu, S. Realegeno, H.-M. Lee, S. R. Krutzik, M. Schenk, P. A. Sieling, et al. (2011)
Science Translational Medicine 3, 104ra102
   Abstract »    Full Text »    PDF »
Silencing Suppressor of Cytokine Signaling-1 (SOCS1) in Macrophages Improves Mycobacterium tuberculosis Control in an Interferon-{gamma} (IFN-{gamma})-dependent Manner.
B. Carow, X. qun Ye, D. Gavier-Widen, S. Bhuju, W. Oehlmann, M. Singh, M. Skold, L. Ignatowicz, A. Yoshimura, H. Wigzell, et al. (2011)
J. Biol. Chem. 286, 26873-26887
   Abstract »    Full Text »    PDF »
The mononuclear phagocyte system of the pig as a model for understanding human innate immunity and disease.
L. Fairbairn, R. Kapetanovic, D. P. Sester, and D. A. Hume (2011)
J. Leukoc. Biol. 89, 855-871
   Abstract »    Full Text »    PDF »
TLR engagement prior to virus infection influences MHC-I antigen presentation in an epitope-dependent manner as a result of nitric oxide release.
S. Siddiqui, A. Alatery, A. Kus, and S. Basta (2011)
J. Leukoc. Biol. 89, 457-468
   Abstract »    Full Text »    PDF »
T-cell cytokines differentially control human monocyte antimicrobial responses by regulating vitamin D metabolism.
K. Edfeldt, P. T. Liu, R. Chun, M. Fabri, M. Schenk, M. Wheelwright, C. Keegan, S. R. Krutzik, J. S. Adams, M. Hewison, et al. (2010)
PNAS 107, 22593-22598
   Abstract »    Full Text »    PDF »
A Novel Pathway for Inducible Nitric-oxide Synthase Activation through Inflammasomes.
C. L. Buzzo, J. C. Campopiano, L. M. Massis, S. L. Lage, A. A. Cassado, R. Leme-Souza, L. D. Cunha, M. Russo, D. S. Zamboni, G. P. Amarante-Mendes, et al. (2010)
J. Biol. Chem. 285, 32087-32095
   Abstract »    Full Text »    PDF »
Mycobacterium tuberculosis and TLR2 Agonists Inhibit Induction of Type I IFN and Class I MHC Antigen Cross Processing by TLR9.
D. P. Simmons, D. H. Canaday, Y. Liu, Q. Li, A. Huang, W. H. Boom, and C. V. Harding (2010)
J. Immunol. 185, 2405-2415
   Abstract »    Full Text »    PDF »
Influence of serum on the immune recognition of a synthetic lipopeptide mimetic of the 19-kDa lipoprotein from Mycobacterium tuberculosis.
A. B. Schromm, N. Reiling, J. Howe, K.-H. Wiesmuller, M. Roessle, and K. Brandenburg (2010)
Innate Immunity 16, 213-225
   Abstract »    PDF »
The Role of TLR4 in Photoreceptor {alpha}A Crystallin Upregulation during Early Experimental Autoimmune Uveitis.
S. Saraswathy, A. M. Nguyen, and N. A. Rao (2010)
Invest. Ophthalmol. Vis. Sci. 51, 3680-3686
   Abstract »    Full Text »    PDF »
Transient role of CD4+CD25+ regulatory T cells in mycobacterial infection in mice.
Y. Ozeki, I. Sugawara, T. Udagawa, T. Aoki, M. Osada-Oka, Y. Tateishi, H. Hisaeda, Y. Nishiuchi, N. Harada, K. Kobayashi, et al. (2010)
Int. Immunol. 22, 179-189
   Abstract »    Full Text »    PDF »
CD14+ Monocytes Are Vulnerable and Functionally Impaired Under Endoplasmic Reticulum Stress in Patients With Type 2 Diabetes.
T. Komura, Y. Sakai, M. Honda, T. Takamura, K. Matsushima, and S. Kaneko (2010)
Diabetes 59, 634-643
   Abstract »    Full Text »    PDF »
CD23 Mediates Antimycobacterial Activity of Human Macrophages.
M. D. Mossalayi, I. Vouldoukis, M. Mamani-Matsuda, T. Kauss, J. Guillon, J. Maugein, D. Moynet, J. Rambert, V. Desplat, D. Mazier, et al. (2009)
Infect. Immun. 77, 5537-5542
   Abstract »    Full Text »    PDF »
Cysteinyl-Leukotriene Receptor Type 1 Expression and Function Is Down-Regulated during Monocyte-Derived Dendritic Cell Maturation with Zymosan: Involvement of IL-10 and Prostaglandins.
M. Thivierge, J. Stankova, and M. Rola-Pleszczynski (2009)
J. Immunol. 183, 6778-6787
   Abstract »    Full Text »    PDF »
A role for glycogen synthase kinase-3 in antagonizing mycobacterial immune evasion by negatively regulating IL-10 induction.
M. M. P. Chan, B. K. W. Cheung, J. C. B. Li, L. L. Y. Chan, and A. S. Y. Lau (2009)
J. Leukoc. Biol. 86, 283-291
   Abstract »    Full Text »    PDF »
Alternative Strategies for Toxicity Testing of Species-Specific Biopharmaceuticals.
J. L. Bussiere, P. Martin, M. Horner, J. Couch, M. Flaherty, L. Andrews, J. Beyer, and C. Horvath (2009)
International Journal of Toxicology 28, 230-253
   Abstract »    Full Text »    PDF »
The Role of Toll-like Receptor 2 in Survival Strategies of Mycobacterium tuberculosis in Macrophage Phagosomes.
A. YOSHIDA, H. INAGAWA, C. KOHCHI, T. NISHIZAWA, and G.-I. SOMA (2009)
Anticancer Res 29, 907-910
   Abstract »    Full Text »    PDF »
IFN-{beta} Impairs Superoxide-Dependent Parasite Killing in Human Macrophages: Evidence for a Deleterious Role of SOD1 in Cutaneous Leishmaniasis.
R. Khouri, A. Bafica, M. d. P. P. Silva, A. Noronha, J.-P. Kolb, J. Wietzerbin, A. Barral, M. Barral-Netto, and J. Van Weyenbergh (2009)
J. Immunol. 182, 2525-2531
   Abstract »    Full Text »    PDF »
T-cell intrinsic expression of MyD88 is required for sustained expansion of the virus-specific CD8+ T-cell population in LCMV-infected mice.
C. Bartholdy, J. E. Christensen, M. Grujic, J. P. Christensen, and A. R. Thomsen (2009)
J. Gen. Virol. 90, 423-431
   Abstract »    Full Text »    PDF »
IL-15 Links TLR2/1-Induced Macrophage Differentiation to the Vitamin D-Dependent Antimicrobial Pathway.
S. R. Krutzik, M. Hewison, P. T. Liu, J. A. Robles, S. Stenger, J. S. Adams, and R. L. Modlin (2008)
J. Immunol. 181, 7115-7120
   Abstract »    Full Text »    PDF »
Toll-like receptor ligands synergize through distinct dendritic cell pathways to induce T cell responses: Implications for vaccines.
Q. Zhu, C. Egelston, A. Vivekanandhan, S. Uematsu, S. Akira, D. M. Klinman, I. M. Belyakov, and J. A. Berzofsky (2008)
PNAS 105, 16260-16265
   Abstract »    Full Text »    PDF »
MyD88 Plays a Critical T Cell-Intrinsic Role in Supporting CD8 T Cell Expansion during Acute Lymphocytic Choriomeningitis Virus Infection.
A. H. Rahman, W. Cui, D. F. LaRosa, D. K. Taylor, J. Zhang, D. R. Goldstein, E. J. Wherry, S. M. Kaech, and L. A. Turka (2008)
J. Immunol. 181, 3804-3810
   Abstract »    Full Text »    PDF »
Importance of TLR2 in Early Innate Immune Response to Acute Pulmonary Infection with Porphyromonas gingivalis in Mice.
G. Hajishengallis, M. Wang, G. J. Bagby, and S. Nelson (2008)
J. Immunol. 181, 4141-4149
   Abstract »    Full Text »    PDF »
Vitamin D Signaling, Infectious Diseases, and Regulation of Innate Immunity.
J. H. White (2008)
Infect. Immun. 76, 3837-3843
   Full Text »    PDF »
Animal models of acute lung injury.
G. Matute-Bello, C. W. Frevert, and T. R. Martin (2008)
Am J Physiol Lung Cell Mol Physiol 295, L379-L399
   Abstract »    Full Text »    PDF »
Proteomic Analysis of and Immune Responses to Ehrlichia chaffeensis Lipoproteins.
H. Huang, M. Lin, X. Wang, T. Kikuchi, H. Mottaz, A. Norbeck, and Y. Rikihisa (2008)
Infect. Immun. 76, 3405-3414
   Abstract »    Full Text »    PDF »
Mycobacterial Lipopeptides Elicit CD4+ CTLs in Mycobacterium tuberculosis-Infected Humans.
M. Bastian, T. Braun, H. Bruns, M. Rollinghoff, and S. Stenger (2008)
J. Immunol. 180, 3436-3446
   Abstract »    Full Text »    PDF »
Regulation of MyD88-Dependent Signaling Events by S Nitrosylation Retards Toll-Like Receptor Signal Transduction and Initiation of Acute-Phase Immune Responses.
T. Into, M. Inomata, M. Nakashima, K.-i. Shibata, H. Hacker, and K. Matsushita (2008)
Mol. Cell. Biol. 28, 1338-1347
   Abstract »    Full Text »    PDF »
Antigen Capture of Porphyromonas gingivalis by Human Macrophages Is Enhanced but Killing and Antigen Presentation Are Reduced by Endotoxin Tolerance.
M. Muthukuru and C. W. Cutler (2008)
Infect. Immun. 76, 477-485
   Abstract »    Full Text »    PDF »
The Proinflammatory Cytokine Response to Chlamydia trachomatis Elementary Bodies in Human Macrophages Is Partly Mediated by a Lipoprotein, the Macrophage Infectivity Potentiator, through TLR2/TLR1/TLR6 and CD14.
S. Bas, L. Neff, M. Vuillet, U. Spenato, T. Seya, M. Matsumoto, and C. Gabay (2008)
J. Immunol. 180, 1158-1168
   Abstract »    Full Text »    PDF »
Saccharomyces boulardii decreases inflammation and intestinal colonization by Candida albicans in a mouse model of chemically-induced colitis.
S. Jawhara and D. Poulain (2007)
Med Mycol 45, 691-700
   Abstract »    Full Text »    PDF »
Progression of Pulmonary Tuberculosis and Efficiency of Bacillus Calmette-Guerin Vaccination Are Genetically Controlled via a Common sst1-Mediated Mechanism of Innate Immunity.
B.-S. Yan, A. V. Pichugin, O. Jobe, L. Helming, E. B. Eruslanov, J. A. Gutierrez-Pabello, M. Rojas, Y. V. Shebzukhov, L. Kobzik, and I. Kramnik (2007)
J. Immunol. 179, 6919-6932
   Abstract »    Full Text »    PDF »
Nucleotide-Binding Oligomerization Domain Protein 2-Deficient Mice Control Infection with Mycobacterium tuberculosis.
S. Gandotra, S. Jang, P. J. Murray, P. Salgame, and S. Ehrt (2007)
Infect. Immun. 75, 5127-5134
   Abstract »    Full Text »    PDF »
Acylation Determines the Toll-like receptor (TLR)-dependent Positive Versus TLR2-, Mannose Receptor-, and SIGNR1-independent Negative Regulation of Pro-inflammatory Cytokines by Mycobacterial Lipomannan.
E. Doz, S. Rose, J. Nigou, M. Gilleron, G. Puzo, F. Erard, B. Ryffel, and V. F. J. Quesniaux (2007)
J. Biol. Chem. 282, 26014-26025
   Abstract »    Full Text »    PDF »
Aggregating Phenotype in Lactobacillus crispatus Determines Intestinal Colonization and TLR2 and TLR4 Modulation in Murine Colonic Mucosa.
S. Voltan, I. Castagliuolo, M. Elli, S. Longo, P. Brun, R. D'Inca, A. Porzionato, V. Macchi, G. Palu, G. C. Sturniolo, et al. (2007)
Clin. Vaccine Immunol. 14, 1138-1148
   Abstract »    Full Text »    PDF »
Repeated social defeat increases the bactericidal activity of splenic macrophages through a Toll-like receptor-dependent pathway.
M. T. Bailey, H. Engler, N. D. Powell, D. A. Padgett, and J. F. Sheridan (2007)
Am J Physiol Regulatory Integrative Comp Physiol 293, R1180-R1190
   Abstract »    Full Text »    PDF »
Cutting Edge: Vitamin D-Mediated Human Antimicrobial Activity against Mycobacterium tuberculosis Is Dependent on the Induction of Cathelicidin.
P. T. Liu, S. Stenger, D. H. Tang, and R. L. Modlin (2007)
J. Immunol. 179, 2060-2063
   Abstract »    Full Text »    PDF »
IL-1 Receptor-Mediated Signal Is an Essential Component of MyD88-Dependent Innate Response to Mycobacterium tuberculosis Infection.
C. M. Fremond, D. Togbe, E. Doz, S. Rose, V. Vasseur, I. Maillet, M. Jacobs, B. Ryffel, and V. F. J. Quesniaux (2007)
J. Immunol. 179, 1178-1189
   Abstract »    Full Text »    PDF »
Molecular Characterization and Subcellular Localization of Macrophage Infectivity Potentiator, a Chlamydia trachomatis Lipoprotein.
L. Neff, S. Daher, P. Muzzin, U. Spenato, F. Gulacar, C. Gabay, and S. Bas (2007)
J. Bacteriol. 189, 4739-4748
   Abstract »    Full Text »    PDF »
Lipoprotein synthesis in mycobacteria.
M. Rezwan, T. Grau, A. Tschumi, and P. Sander (2007)
Microbiology 153, 652-658
   Abstract »    Full Text »    PDF »
Mycobacterium tuberculosis Subverts Innate Immunity to Evade Specific Effectors.
C. Loeuillet, F. Martinon, C. Perez, M. Munoz, M. Thome, and P. R. Meylan (2006)
J. Immunol. 177, 6245-6255
   Abstract »    Full Text »    PDF »
Vitamin D3-Triggered Antimicrobial Response--Another Pleiotropic Effect beyond Mineral and Bone Metabolism: Toll-Like Receptor Triggering of a Vitamin D-Mediated Human Antimicrobial Response. Science 311: 1770-1773, 2006.
P.T. Liu, S. Stenger, H. Li, L. Wenzel, B.H. Tan, S.R. Krutzik, M.T. Ochoa, J. Schauber, K. Wu, C. Meinken, et al. (2006)
J. Am. Soc. Nephrol. 17, 2949-2953
   Full Text »    PDF »
Baculovirus-Derived Human Immunodeficiency Virus Type 1 Virus-Like Particles Activate Dendritic Cells and Induce Ex Vivo T-Cell Responses.
L. Buonaguro, M. L. Tornesello, M. Tagliamonte, R. C. Gallo, L. X. Wang, R. Kamin-Lewis, S. Abdelwahab, G. K. Lewis, and F. M. Buonaguro (2006)
J. Virol. 80, 9134-9143
   Abstract »    Full Text »    PDF »
An {alpha}-Glucan of Pseudallescheria boydii Is Involved in Fungal Phagocytosis and Toll-like Receptor Activation.
V. C. B. Bittencourt, R. T. Figueiredo, R. B. da Silva, D. S. Mourao-Sa, P. L. Fernandez, G. L. Sassaki, B. Mulloy, M. T. Bozza, and E. Barreto-Bergter (2006)
J. Biol. Chem. 281, 22614-22623
   Abstract »    Full Text »    PDF »
Protection from lethal septic peritonitis by neutralizing the biological function of interleukin 27.
S. Wirtz, I. Tubbe, P. R. Galle, H. J. Schild, M. Birkenbach, R. S. Blumberg, and M. F. Neurath (2006)
J. Exp. Med. 203, 1875-1881
   Abstract »    Full Text »    PDF »
The Transforming Growth Factor-beta-Smad3/4 Signaling Pathway Acts as a Positive Regulator for TLR2 Induction by Bacteria via a Dual Mechanism Involving Functional Cooperation with NF-{kappa}B and MAPK Phosphatase 1-dependent Negative Cross-talk with p38 MAPK.
F. Mikami, J. H. Lim, H. Ishinaga, U.-H. Ha, H. Gu, T. Koga, H. Jono, H. Kai, and J.-D. Li (2006)
J. Biol. Chem. 281, 22397-22408
   Abstract »    Full Text »    PDF »
Role of iNOS in Human Host Defense.
C. Nathan;, P. Liu, J. S. Adams, and R. L. Modlin (2006)
Science 312, 1874b-1875b
   Full Text »    PDF »
Topical Application of Escherichia coli-Vectored Vaccine as a Simple Method for Eliciting Protective Immunity.
J. Zhang, Z. Shi, F.-k. Kong, E. Jex, Z. Huang, J. M. Watt, K. R. Van Kampen, and D.-c. C. Tang (2006)
Infect. Immun. 74, 3607-3617
   Abstract »    Full Text »    PDF »
Macrophage nutriprive antimicrobial mechanisms.
R. Appelberg (2006)
J. Leukoc. Biol. 79, 1117-1128
   Abstract »    Full Text »    PDF »
Toll-Like Receptor Triggering of a Vitamin D-Mediated Human Antimicrobial Response.
P. T. Liu, S. Stenger, H. Li, L. Wenzel, B. H. Tan, S. R. Krutzik, M. T. Ochoa, J. Schauber, K. Wu, C. Meinken, et al. (2006)
Science 311, 1770-1773
   Abstract »    Full Text »    PDF »
Innate Immune Signaling and Porphyromonas gingivalis-accelerated Atherosclerosis.
F.C. Gibson III, H. Yumoto, Y. Takahashi, H.-H. Chou, and C.A. Genco (2006)
Journal of Dental Research 85, 106-121
   Abstract »    Full Text »    PDF »
TLR9 regulates Th1 responses and cooperates with TLR2 in mediating optimal resistance to Mycobacterium tuberculosis.
A. Bafica, C. A. Scanga, C. G. Feng, C. Leifer, A. Cheever, and A. Sher (2005)
J. Exp. Med. 202, 1715-1724
   Abstract »    Full Text »    PDF »
Human Airway Epithelial Cells Sense Pseudomonas aeruginosa Infection via Recognition of Flagellin by Toll-Like Receptor 5.
Z. Zhang, J.-P. Louboutin, D. J. Weiner, J. B. Goldberg, and J. M. Wilson (2005)
Infect. Immun. 73, 7151-7160
   Abstract »    Full Text »    PDF »
Immunological control of tuberculosis: role of tumour necrosis factor and more.
S Stenger (2005)
Ann Rheum Dis 64, iv24-iv28
   Abstract »    Full Text »    PDF »
Epidermal Growth Factor Receptor Acts as a Negative Regulator for Bacterium Nontypeable Haemophilus influenzae-induced Toll-like Receptor 2 Expression via an Src-dependent p38 Mitogen-activated Protein Kinase Signaling Pathway.
F. Mikami, H. Gu, H. Jono, A. Andalibi, H. Kai, and J.-D. Li (2005)
J. Biol. Chem. 280, 36185-36194
   Abstract »    Full Text »    PDF »
Activation and Mitogen-Activated Protein Kinase Regulation of Transcription Factors Ets and NF-{kappa}B in Mycobacterium-Infected Macrophages and Role of These Factors in Tumor Necrosis Factor Alpha and Nitric Oxide Synthase 2 Promoter Function.
S.-B. Lee and J. S. Schorey (2005)
Infect. Immun. 73, 6499-6507
   Abstract »    Full Text »    PDF »
Effect of Deletion or Overexpression of the 19-Kilodalton Lipoprotein Rv3763 on the Innate Response to Mycobacterium tuberculosis.
G. R. Stewart, K. A. Wilkinson, S. M. Newton, S. M. Sullivan, O. Neyrolles, J. R. Wain, J. Patel, K.-L. Pool, D. B. Young, and R. J. Wilkinson (2005)
Infect. Immun. 73, 6831-6837
   Abstract »    Full Text »    PDF »
DNA Augments Antigenicity of Mycobacterial DNA-Binding Protein 1 and Confers Protection against Mycobacterium tuberculosis Infection in Mice.
S. Matsumoto, M. Matsumoto, K. Umemori, Y. Ozeki, M. Furugen, T. Tatsuo, Y. Hirayama, S. Yamamoto, T. Yamada, and K. Kobayashi (2005)
J. Immunol. 175, 441-449
   Abstract »    Full Text »    PDF »
Mycobacterium Tuberculosis Heat Shock Proteins Use Diverse Toll-like Receptor Pathways to Activate Pro-inflammatory Signals.
Y. Bulut, K. S. Michelsen, L. Hayrapetian, Y. Naiki, R. Spallek, M. Singh, and M. Arditi (2005)
J. Biol. Chem. 280, 20961-20967
   Abstract »    Full Text »    PDF »
Regulated recruitment of DC-SIGN to cell-cell contact regions during zymosan-induced human dendritic cell aggregation.
G. de la Rosa, M. Yanez-Mo, R. Samaneigo, D. Serrano-Gomez, L. Martinez-Munoz, E. Fernandez-Ruiz, N. Longo, F. Sanchez-Madrid, A. L. Corbi, and P. Sanchez-Mateos (2005)
J. Leukoc. Biol. 77, 699-709
   Abstract »    Full Text »    PDF »
An Epidermal Barrier Wound Repair Pathway in Drosophila Is Mediated by grainy head.
K. A. Mace, J. C. Pearson, and W. McGinnis (2005)
Science 308, 381-385
   Abstract »    Full Text »    PDF »
Identification and Functional Characterization of Chicken Toll-Like Receptor 5 Reveals a Fundamental Role in the Biology of Infection with Salmonella enterica Serovar Typhimurium.
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. (2005)
Infect. Immun. 73, 2344-2350
   Abstract »    Full Text »    PDF »
The physiological regulation of toll-like receptor expression and function in humans.
G. I Lancaster, Q. Khan, P. Drysdale, F. Wallace, A. E Jeukendrup, M. T Drayson, and M. Gleeson (2005)
J. Physiol. 563, 945-955
   Abstract »    Full Text »    PDF »
A Soluble Form of the Triggering Receptor Expressed on Myeloid Cells-1 Modulates the Inflammatory Response in Murine Sepsis.
S. Gibot, M.-N. Kolopp-Sarda, M.-C. Bene, P.-E. Bollaert, A. Lozniewski, F. Mory, B. Levy, and G. C. Faure (2004)
J. Exp. Med. 200, 1419-1426
   Abstract »    Full Text »    PDF »
Long-Term Control of Mycobacterium bovis BCG Infection in the Absence of Toll-Like Receptors (TLRs): Investigation of TLR2-, TLR6-, or TLR2-TLR4-Deficient Mice.
D. Nicolle, C. Fremond, X. Pichon, A. Bouchot, I. Maillet, B. Ryffel, and V. J. F. Quesniaux (2004)
Infect. Immun. 72, 6994-7004
   Abstract »    Full Text »    PDF »
Prolonged Toll-Like Receptor Signaling by Mycobacterium tuberculosis and Its 19-Kilodalton Lipoprotein Inhibits Gamma Interferon-Induced Regulation of Selected Genes in Macrophages.
R. K. Pai, M. E. Pennini, A. A. R. Tobian, D. H. Canaday, W. H. Boom, and C. V. Harding (2004)
Infect. Immun. 72, 6603-6614
   Abstract »    Full Text »    PDF »
Microarray Analysis Reveals Induction of Lipoprotein Genes in Mucoid Pseudomonas aeruginosa: Implications for Inflammation in Cystic Fibrosis.
A. M. Firoved, W. Ornatowski, and V. Deretic (2004)
Infect. Immun. 72, 5012-5018
   Abstract »    Full Text »    PDF »
Mitogenicity of the Recombinant Mycobacterial 27-Kilodalton Lipoprotein Is Not Connected to Its Antiprotective Effect.
A.-H. Hovav, L. Davidovitch, G. Nussbaum, J. Mullerad, Y. Fishman, and H. Bercovier (2004)
Infect. Immun. 72, 3383-3390
   Abstract »    Full Text »    PDF »
The Novel Cyclophilin-Binding Drug Sanglifehrin A Specifically Affects Antigen Uptake Receptor Expression and Endocytic Capacity of Human Dendritic Cells.
A. M. Woltman, N. Schlagwein, S. W. van der Kooij, and C. van Kooten (2004)
J. Immunol. 172, 6482-6489
   Abstract »    Full Text »    PDF »
IMMUNOLOGY: The Bell Tolls for Phagosome Maturation.
C. Watts (2004)
Science 304, 976-977
   Abstract »    Full Text »    PDF »
Toll-Like Receptor 2 (TLR2)-Dependent-Positive and TLR2-Independent-Negative Regulation of Proinflammatory Cytokines by Mycobacterial Lipomannans.
V. J. Quesniaux, D. M. Nicolle, D. Torres, L. Kremer, Y. Guerardel, J. Nigou, G. Puzo, F. Erard, and B. Ryffel (2004)
J. Immunol. 172, 4425-4434
   Abstract »    Full Text »    PDF »
Toll-like receptor 4 plays a protective role in pulmonary tuberculosis in mice.
J. Branger, J. C. Leemans, S. Florquin, S. Weijer, P. Speelman, and T. van der Poll (2004)
Int. Immunol. 16, 509-516
   Abstract »    Full Text »    PDF »
Toll-Like Receptor 2 Plays a Role in the Early Inflammatory Response to Murine Pneumococcal Pneumonia but Does Not Contribute to Antibacterial Defense.
S. Knapp, C. W. Wieland, C. van 't Veer, O. Takeuchi, S. Akira, S. Florquin, and T. van der Poll (2004)
J. Immunol. 172, 3132-3138
   Abstract »    Full Text »    PDF »
The Arg753Gln polymorphism of the human Toll-like receptor 2 gene in tuberculosis disease.
A.C. Ogus, B. Yoldas, T. Ozdemir, A. Uguz, S. Olcen, I. Keser, M. Coskun, A. Cilli, and O. Yegin (2004)
Eur. Respir. J. 23, 219-223
   Abstract »    Full Text »    PDF »
Toll-like Receptors Induce a Phagocytic Gene Program through p38.
S. E. Doyle, R. M. O'Connell, G. A. Miranda, S. A. Vaidya, E. K. Chow, P. T. Liu, S. Suzuki, N. Suzuki, R. L. Modlin, W.-C. Yeh, et al. (2004)
J. Exp. Med. 199, 81-90
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882