title: Role of Interleukin 36γ in Host Defense Against Tuberculosis.
abstract: Tuberculosis remains a major killer worldwide, not the least because of our incomplete knowledge of protective and pathogenic immune mechanism. The roles of the interleukin 1 (IL-1) and interleukin 18 pathways in host defense are well established, as are their regulation through the inflammasome complex. In contrast, the regulation of interleukin 36γ (IL-36γ), a recently described member of the IL-1 family, and its immunological relevance in host defense remain largely unknown. Here we show that Mycobacterium tuberculosis infection of macrophages induces IL-36γ production in a 2-stage-regulated fashion. In the first stage, microbial ligands trigger host Toll-like receptor and MyD88-dependent pathways, leading to IL-36γ secretion. In the second stage, endogenous IL-1β and interleukin 18 further amplify IL-36γ synthesis. The relevance of this cytokine in the control of M. tuberculosis is demonstrated by IL-36γ-induced antimicrobial peptides and IL-36 receptor-dependent restriction of M. tuberculosis growth. Thus, we provide first insight into the induction and regulation of the proinflammatory cytokine IL-36γ during tuberculosis.
authors.affiliation: Department of Immunology, Max Planck Institute for Infection Biology, and ZIBI Graduate School Berlin, Germany.
authors.forename: Fadhil
authors.initials: F
authors.lastname: Ahsan
authors.affiliation: Department of Immunology, Max Planck Institute for Infection Biology, and.
authors.forename: Pedro
authors.initials: P
authors.lastname: Moura-Alves
authors.affiliation: Department of Immunology, Max Planck Institute for Infection Biology, and.
authors.forename: Ute
authors.initials: U
authors.lastname: Guhlich-Bornhof
authors.affiliation: Department of Immunology, Max Planck Institute for Infection Biology, and.
authors.forename: Marion
authors.initials: M
authors.lastname: Klemm
authors.affiliation: Department of Immunology, Max Planck Institute for Infection Biology, and.
authors.forename: Stefan H E
authors.initials: SH
authors.lastname: Kaufmann
authors.affiliation: Department of Immunology, Max Planck Institute for Infection Biology, and.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Maertzdorf
mesh_terms: D000818:Animals; D002460:Cell Line; D006801:Humans; D007375:Interleukin-1 / Q000172:deficiency / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology*
chemical_list: C508589:IL36G protein, human; D007375:Interleukin-1
keywords: IL-36γ; Mycobacterium tuberculosis; TLR; antimicrobial peptide; inflammasome