Limited Contribution of IL-36 versus IL-1 and TNF Pathways in Host Response to Mycobacterial Infection

PLoS One. 2015 May 7;10(5):e0126058. doi: 10.1371/journal.pone.0126058. eCollection 2015.

Abstract

IL-36 cytokines are members of the IL-1 family of cytokines that stimulate dendritic cells and T cells leading to enhanced T helper 1 responses in vitro and in vivo; however, their role in host defense has not been fully addressed thus far. The objective of this study was to examine the role of IL-36R signaling in the control of mycobacterial infection, using models of systemic attenuated M. bovis BCG infection and virulent aerogenic M. tuberculosis infection. IL-36γ expression was increased in the lung of M. bovis BCG infected mice. However, IL-36R deficient mice infected with M. bovis BCG showed similar survival and control of the infection as compared to wild-type mice, although their lung pathology and CXCL1 response were transiently different. While highly susceptible TNF-α deficient mice succumbed with overwhelming M. tuberculosis infection, and IL-1RI deficient mice showed intermediate susceptibility, IL-36R-deficient mice controlled the infection, with bacterial burden, lung inflammation and pathology, similar to wild-type controls. Therefore, IL-36R signaling has only limited influence in the control of mycobacterial infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Host-Pathogen Interactions*
  • Interleukin-1 / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mycobacterium Infections / metabolism*
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • Interleukin-1
  • Tumor Necrosis Factor-alpha
  • interleukin-36, mouse

Grant support

This work was supported by grants from the Swiss National Science Foundation (310030_152638 to CG, 310030_134691 to GP, 310030_46833 to IG), LPG to IG, the Rheumasearch Foundation, the Institute of Arthritis Research, the CNRS International Associated Laboratory "TB IMMUNITY" (LIA N°236), and the Region Centre (No 2013-00085470) (France). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.