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- Title
Role of Interleukin 36γ in Host Defense Against Tuberculosis.
- Authors
Ahsan, Fadhil; Moura-Alves, Pedro; Guhlich-Bornhof, Ute; Klemm, Marion; Kaufmann, Stefan H. E.; Maertzdorf, Jeroen
- 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.
- Subjects
TUBERCULOSIS diagnosis; TUBERCULOSIS patients; TUBERCULOSIS prevention; MYCOBACTERIUM tuberculosis; INTERLEUKIN-1; ANIMALS; CELL lines; MACROPHAGES; MICE; TUBERCULOSIS
- Publication
Journal of Infectious Diseases, 2016, Vol 214, Issue 3, p464
- ISSN
0022-1899
- Publication type
journal article
- DOI
10.1093/infdis/jiw152