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Cutting Edge |
,
* Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;
Section of Immunobiology, Yale University School of Medicine and
Howard Hughes Medical Institute, New Haven, CT 06520; and
Department of Microbiology and Immunology, Cornell University College of Veterinary Medicine, Ithaca, NY 14853
Host resistance to the intracellular protozoan Toxoplasma gondii is highly dependent on early IL-12 production by APC. We demonstrate here that both host resistance and T. gondii-induced IL-12 production are dramatically reduced in mice lacking the adaptor molecule MyD88, an important signaling element used by Toll-like receptor (TLR) family members. Infection of MyD88-deficient mice with T. gondii resulted in uncontrolled parasite replication and greatly reduced plasma IL-12 levels. Defective IL-12 responses to T. gondii Ags (soluble tachyzoite Ag (STAg)) were observed in MyD88-/- peritoneal macrophages, neutrophils, and splenic dendritic cells (DC). In contrast, DC from TLR2- or TLR4-deficient animals developed normal IL-12 responses to STAg. In vivo treatment with pertussis toxin abolished the residual IL-12 response displayed by STAg-stimulated DC from MyD88-/- mice. Taken together, these data suggest that the induction of IL-12 by T. gondii depends on a unique mechanism involving both MyD88 and G protein-coupled signaling pathways.
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M. A. Campos, M. Closel, E. P. Valente, J. E. Cardoso, S. Akira, J. I. Alvarez-Leite, C. Ropert, and R. T. Gazzinelli Impaired Production of Proinflammatory Cytokines and Host Resistance to Acute Infection with Trypanosoma cruzi in Mice Lacking Functional Myeloid Differentiation Factor 88 J. Immunol., February 1, 2004; 172(3): 1711 - 1718. [Abstract] [Full Text] [PDF]
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A. Debus, J. Glasner, M. Rollinghoff, and A. Gessner High Levels of Susceptibility and T Helper 2 Response in MyD88-Deficient Mice Infected with Leishmania major Are Interleukin-4 Dependent Infect. Immun., December 1, 2003; 71(12): 7215 - 7218. [Abstract] [Full Text] [PDF]
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S. Bennouna, S. K. Bliss, T. J. Curiel, and E. Y. Denkers Cross-Talk in the Innate Immune System: Neutrophils Instruct Recruitment and Activation of Dendritic Cells during Microbial Infection J. Immunol., December 1, 2003; 171(11): 6052 - 6058. [Abstract] [Full Text] [PDF]
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C. G. Feng, C. A. Scanga, C. M. Collazo-Custodio, A. W. Cheever, S. Hieny, P. Caspar, and A. Sher Mice Lacking Myeloid Differentiation Factor 88 Display Profound Defects in Host Resistance and Immune Responses to Mycobacterium avium Infection Not Exhibited by Toll-Like Receptor 2 (TLR2)- and TLR4-Deficient Animals J. Immunol., November 1, 2003; 171(9): 4758 - 4764. [Abstract] [Full Text] [PDF]
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S. Shi, C. Nathan, D. Schnappinger, J. Drenkow, M. Fuortes, E. Block, A. Ding, T. R. Gingeras, G. Schoolnik, S. Akira, et al. MyD88 Primes Macrophages for Full-Scale Activation by Interferon-{gamma} yet Mediates Few Responses to Mycobacterium tuberculosis J. Exp. Med., October 6, 2003; 198(7): 987 - 997. [Abstract] [Full Text] [PDF]
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H.-S. Mun, F. Aosai, K. Norose, M. Chen, L.-X. Piao, O. Takeuchi, S. Akira, H. Ishikura, and A. Yano TLR2 as an essential molecule for protective immunity against Toxoplasma gondii infection Int. Immunol., September 1, 2003; 15(9): 1081 - 1087. [Abstract] [Full Text] [PDF]
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F. Debierre-Grockiego, N. Azzouz, J. Schmidt, J.-F. Dubremetz, H. Geyer, R. Geyer, R. Weingart, R. R. Schmidt, and R. T. Schwarz Roles of Glycosylphosphatidylinositols of Toxoplasma gondii: INDUCTION OF TUMOR NECROSIS FACTOR-{alpha} PRODUCTION IN MACROPHAGES J. Biol. Chem., August 29, 2003; 278(35): 32987 - 32993. [Abstract] [Full Text] [PDF]
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A. Bafica, C. A. Scanga, M. L. Schito, S. Hieny, and A. Sher Cutting Edge: In Vivo Induction of Integrated HIV-1 Expression by Mycobacteria Is Critically Dependent on Toll-Like Receptor 2 J. Immunol., August 1, 2003; 171(3): 1123 - 1127. [Abstract] [Full Text] [PDF]
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L.-Y. Huang, J. Aliberti, C. A. Leifer, D. M. Segal, A. Sher, D. T. Golenbock, and B. Golding Heat-Killed Brucella abortus Induces TNF and IL-12p40 by Distinct MyD88-Dependent Pathways: TNF, Unlike IL-12p40 Secretion, Is Toll-Like Receptor 2 Dependent J. Immunol., August 1, 2003; 171(3): 1441 - 1446. [Abstract] [Full Text] [PDF]
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T. Bartfai, M. M. Behrens, S. Gaidarova, J. Pemberton, A. Shivanyuk, and J. Rebek Jr A low molecular weight mimic of the Toll/IL-1 receptor/resistance domain inhibits IL-1 receptor-mediated responses PNAS, June 24, 2003; 100(13): 7971 - 7976. [Abstract] [Full Text] [PDF]
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E. Muraille, C. De Trez, M. Brait, P. De Baetselier, O. Leo, and Y. Carlier Genetically Resistant Mice Lacking MyD88-Adapter Protein Display a High Susceptibility to Leishmania major Infection Associated with a Polarized Th2 Response J. Immunol., April 15, 2003; 170(8): 4237 - 4241. [Abstract] [Full Text] [PDF]
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A. D. Edwards, S. P. Manickasingham, R. Sporri, S. S. Diebold, O. Schulz, A. Sher, T. Kaisho, S. Akira, and C. Reis e Sousa Microbial Recognition Via Toll-Like Receptor-Dependent and -Independent Pathways Determines the Cytokine Response of Murine Dendritic Cell Subsets to CD40 Triggering J. Immunol., October 1, 2002; 169(7): 3652 - 3660. [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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H. Weighardt, S. Kaiser-Moore, R. M. Vabulas, C. J. Kirschning, H. Wagner, and B. Holzmann Cutting Edge: Myeloid Differentiation Factor 88 Deficiency Improves Resistance Against Sepsis Caused by Polymicrobial Infection J. Immunol., September 15, 2002; 169(6): 2823 - 2827. [Abstract] [Full Text] [PDF]
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