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* First Department of Surgery and
Department of Immunology and Medical Zoology, Hyogo College of Medicine, Nishinomiya, Japan;
Laboratory of Molecular Immunology, Department of Molecular Biology and Immunology, National Institute for Agrobiological Sciences, Tsukuba, Japan;
Department of Host Defenses, Research Institute for Microbial Diseases, Osaka University, Suita, Japan; and
¶ Core Research for Evolutional Science and Technology, Japan Science and Technology Corp., Tokyo, Japan
Listeria monocytogenes (LM), a facultative
intracellular Gram-positive bacterium, often causes lethal infection of
the host. In this study we investigated the molecular mechanism
underlying LM eradication in the early phase of infection. Upon
infection with LM, both IL-12 and IL-18 were produced, and then they
synergistically induced IFN-
production, leading to normal LM
clearance in the host. IFN- knockout (KO) mice were highly
susceptible to LM infection. IL-12/IL-18 double knockout mice were also
highly susceptible. Their susceptibility was less than that of IFN-
KO mice, but more than that of single IL-12 or IL-18 KO mice. Mice
deficient in myeloid differentiation factor 88 (MyD88), an essential
adaptor molecule used by signal transduction pathways of all members of
the Toll-like receptor (TLR) family, showed an inability to produce
IL-12 and IFN- following LM infection and were most susceptible to
LM. Furthermore, MyD88-deficient, but not IFN--deficient, Kupffer
cells could not produce TNF-
in response to LM in vitro, indicating
the importance of MyD88-dependent TNF- production for host defense.
As TLR2 KO, but not TLR4 KO, mice showed partial impairment in their
capacity to produce IL-12, IFN-, and TNF-, TLR2 activation partly
contributed to the induction of IL-12-mediated IFN- production.
These results indicated a critical role for TLRs/MyD88-dependent
IL-12/TNF- production and for IL-12- and IL-18-mediated IFN-
production in early phase clearance of LM.
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J. Schmieg, G. Yang, R. W. Franck, N. Van Rooijen, and M. Tsuji Glycolipid presentation to natural killer T cells differs in an organ-dependent fashion PNAS, January 25, 2005; 102(4): 1127 - 1132. [Abstract] [Full Text] [PDF]
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J. Liu, X. Guan, T. Tamura, K. Ozato, and X. Ma Synergistic Activation of Interleukin-12 p35 Gene Transcription by Interferon Regulatory Factor-1 and Interferon Consensus Sequence-binding Protein J. Biol. Chem., December 31, 2004; 279(53): 55609 - 55617. [Abstract] [Full Text] [PDF]
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H. Hata, T. Yoshimoto, N. Hayashi, T. Hada, and K. Nakanishi IL-18 together with anti-CD3 antibody induces human Th1 cells to produce Th1- and Th2-cytokines and IL-8 Int. Immunol., December 1, 2004; 16(12): 1733 - 1739. [Abstract] [Full Text] [PDF]
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R. Janssen, A. van Wengen, M. A. Hoeve, M. ten Dam, M. van der Burg, J. van Dongen, E. van de Vosse, M. van Tol, R. Bredius, T. H. Ottenhoff, et al. The Same I{kappa}B{alpha} Mutation in Two Related Individuals Leads to Completely Different Clinical Syndromes J. Exp. Med., September 7, 2004; 200(5): 559 - 568. [Abstract] [Full Text] [PDF]
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R. M. O'Connell, S. K. Saha, S. A. Vaidya, K. W. Bruhn, G. A. Miranda, B. Zarnegar, A. K. Perry, B. O. Nguyen, T. F. Lane, T. Taniguchi, et al. Type I Interferon Production Enhances Susceptibility to Listeria monocytogenes Infection J. Exp. Med., August 16, 2004; 200(4): 437 - 445. [Abstract] [Full Text] [PDF]
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D. D. Bolz, R. S. Sundsbak, Y. Ma, S. Akira, C. J. Kirschning, J. F. Zachary, J. H. Weis, and J. J. Weis MyD88 Plays a Unique Role in Host Defense but Not Arthritis Development in Lyme Disease J. Immunol., August 1, 2004; 173(3): 2003 - 2010. [Abstract] [Full Text] [PDF]
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N. Liu, R. R. Montgomery, S. W. Barthold, and L. K. Bockenstedt Myeloid Differentiation Antigen 88 Deficiency Impairs Pathogen Clearance but Does Not Alter Inflammation in Borrelia burgdorferi-Infected Mice Infect. Immun., June 1, 2004; 72(6): 3195 - 3203. [Abstract] [Full Text] [PDF]
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G. Mancuso, A. Midiri, C. Beninati, C. Biondo, R. Galbo, S. Akira, P. Henneke, D. Golenbock, and G. Teti Dual Role of TLR2 and Myeloid Differentiation Factor 88 in a Mouse Model of Invasive Group B Streptococcal Disease J. Immunol., May 15, 2004; 172(10): 6324 - 6329. [Abstract] [Full Text] [PDF]
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M. G. Netea, C. van der Graaf, J. W. M. Van der Meer, and B. J. Kullberg Toll-like receptors and the host defense against microbial pathogens: bringing specificity to the innate-immune system J. Leukoc. Biol., May 1, 2004; 75(5): 749 - 755. [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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C. A. Scanga, A. Bafica, C. G. Feng, A. W. Cheever, S. Hieny, and A. Sher MyD88-Deficient Mice Display a Profound Loss in Resistance to Mycobacterium tuberculosis Associated with Partially Impaired Th1 Cytokine and Nitric Oxide Synthase 2 Expression Infect. Immun., April 1, 2004; 72(4): 2400 - 2404. [Abstract] [Full Text] [PDF]
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S. J. Skerrett, H. D. Liggitt, A. M. Hajjar, and C. B. Wilson Cutting Edge: Myeloid Differentiation Factor 88 Is Essential for Pulmonary Host Defense against Pseudomonas aeruginosa but Not Staphylococcus aureus J. Immunol., March 15, 2004; 172(6): 3377 - 3381. [Abstract] [Full Text] [PDF]
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M. Kursar, H.-W. Mittrucker, M. Koch, A. Kohler, M. Herma, and S. H. E. Kaufmann Protective T cell response against intracellular pathogens in the absence of Toll-like receptor signaling via myeloid differentiation factor 88 Int. Immunol., March 1, 2004; 16(3): 415 - 421. [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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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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L. Lefrancois, A. Marzo, and K. Williams Sustained Response Initiation Is Required for T Cell Clonal Expansion But Not for Effector or Memory Development In Vivo J. Immunol., September 15, 2003; 171(6): 2832 - 2839. [Abstract] [Full Text] [PDF]
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C. Ropert, M. Closel, A. C. L. Chaves, and R. T. Gazzinelli Inhibition of a p38/Stress-Activated Protein Kinase-2-Dependent Phosphatase Restores Function of IL-1 Receptor-Associated Kinase-1 and Reverses Toll-Like Receptor 2- and 4-Dependent Tolerance of Macrophages J. Immunol., August 1, 2003; 171(3): 1456 - 1465. [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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H. Nakano, H. Tsutsui, M. Terada, K. Yasuda, K. Matsui, S. Yumikura-Futatsugi, K.-i. Yamanaka, H. Mizutani, T. Yamamura, and K. Nakanishi Persistent secretion of IL-18 in the skin contributes to IgE response in mice Int. Immunol., May 1, 2003; 15(5): 611 - 621. [Abstract] [Full Text] [PDF]
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