A role for IL-18 in protective immunity against Mycobacterium tuberculosis

Authors

  • Bianca E. Schneider,

    1. London School of Hygiene & Tropical Medicine, Infectious and Tropical Diseases-Immunology, London, UK
    2. Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany
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  • Daniel Korbel,

    1. London School of Hygiene & Tropical Medicine, Infectious and Tropical Diseases-Immunology, London, UK
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  • Kristine Hagens,

    1. Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany
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  • Markus Koch,

    1. Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany
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  • Bärbel Raupach,

    1. Department of Cellular Microbiology, Max Planck Institute for Infection Biology, Berlin, Germany
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  • Jana Enders,

    1. Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany
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  • Stefan H. E. Kaufmann,

    1. Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany
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  • Hans-Willi Mittrücker,

    1. Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany
    2. University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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  • Ulrich E. Schaible

    Corresponding author
    1. London School of Hygiene & Tropical Medicine, Infectious and Tropical Diseases-Immunology, London, UK
    2. Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany
    3. Research Center Borstel, Molecular Infection Research, Borstel, Germany
    • Research Center Borstel, Department of Molecular Infection Research, Parkallee 1, 23845 Borstel, Germany Fax: +49-4537-188-403
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Abstract

Tuberculosis remains the most hazardous bacterial infection worldwide. The causative agent, Mycobacterium tuberculosis, is a facultative intracellular pathogen of resting MΦ. IFN-γ secreted by natural killer, CD4 Th 1 and CD8 T cells upon instruction by IL-12 and -18 activates MΦ to restrict mycobacterial growth. Production of both cytokines is induced by TLR signalling in DC and MΦ. Mice deficient for the TLR adaptor, MyD88, are highly susceptible to M. tuberculosis infection. Shared usage of MyD88 by signalling cascades for TLR and receptors for IL-1 and IL-18 prompted us to revisit the role of IL-18 during experimental infection with M. tuberculosis. We show that mice deficient for IL-18 and MyD88 but not for IL-18 receptor promptly succumbed to M. tuberculosis infection in contrast to WT or TLR-2/-4 double KO mice indicating that lack of IL-18 contributes to the high susceptibility of MyD88 KO mice to M. tuberculosis. Without IL-18, the protective Th1 response was decreased and hence, mycobacterial propagation was favoured. Neutrophil-driven lung immunopathology concomitant with unrestrained growth of tubercle bacilli are most likely responsible for the premature death of IL-18 KO mice. Thus, IL-18 plays a decisive role in protective immunity against tuberculosis.

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