TY - JOUR
T1 - Role of Interleukin 36γ in Host Defense Against Tuberculosis
AU - Ahsan, Fadhil
AU - Moura-Alves, Pedro
AU - Guhlich-Bornhof, Ute
AU - Klemm, Marion
AU - Kaufmann, Stefan H.E.
AU - Maertzdorf, Jeroen
N1 - Publisher Copyright:
© 2016 The Author.
PY - 2016/8/1
Y1 - 2016/8/1
N2 - 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.
AB - 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.
KW - IL-36γ
KW - Mycobacterium tuberculosis
KW - TLR
KW - antimicrobial peptide
KW - inflammasome
UR - http://www.scopus.com/inward/record.url?scp=84981225435&partnerID=8YFLogxK
U2 - 10.1093/infdis/jiw152
DO - 10.1093/infdis/jiw152
M3 - Article
C2 - 27389350
AN - SCOPUS:84981225435
SN - 0022-1899
VL - 214
SP - 464
EP - 474
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 3
ER -