title: A role for IL-18 in protective immunity against Mycobacterium tuberculosis.
abstract: Tuberculosis remains the most hazardous bacterial infection worldwide. The causative agent, Mycobacterium tuberculosis, is a facultative intracellular pathogen of resting MPhi. IFN-gamma secreted by natural killer, CD4 Th 1 and CD8 T cells upon instruction by IL-12 and -18 activates MPhi to restrict mycobacterial growth. Production of both cytokines is induced by TLR signalling in DC and MPhi. 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.
authors: London School of Hygiene & Tropical Medicine, Infectious and Tropical Diseases-Immunology, London, UK.
authors: Bianca E
authors: BE
authors: Schneider
authors: Daniel
authors: D
authors: Korbel
authors: Kristine
authors: K
authors: Hagens
authors: Markus
authors: M
authors: Koch
authors: Bärbel
authors: B
authors: Raupach
authors: Jana
authors: J
authors: Enders
authors: Stefan H E
authors: SH
authors: Kaufmann
authors: Hans-Willi
authors: HW
authors: Mittrücker
authors: Ulrich E
authors: UE
authors: Schaible
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D018925:Chemokines / Q000235:genetics; D016207:Cytokines / Q000235:genetics; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D007109:Immunity / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D020382:Interleukin-18 / Q000235:genetics / Q000276:immunology*; D008168:Lung / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000276:immunology; D020556:Neutrophil Infiltration / Q000276:immunology; D053724:Receptors, Interleukin-18 / Q000235:genetics / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology; D014376:Tuberculosis / Q000235:genetics / Q000276:immunology* / Q000382:microbiology
chemical_list: D018925:Chemokines; D016207:Cytokines; D020382:Interleukin-18; D053594:Myeloid Differentiation Factor 88; D053724:Receptors, Interleukin-18; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D007371:Interferon-gamma