The IL-27 receptor chain WSX-1 differentially regulates antibacterial immunity and survival during experimental tuberculosis

Research output: Contribution to journalArticle

  • External authors:
  • Christoph Hölscher
  • Alexandra Hölscher
  • Takayuki Yoshimoto
  • Hiroki Yoshida
  • Tak Mak
  • Christiaan Saris
  • Stefan Ehlers

Abstract

IL-12 is a potent inducer of IFN-γ production and promotes a protective cell-mediated immune response after Mycobacterium tuberculosis infection. Recently, the IL-12-related cytokine IL-27 was discovered, and WSX-1 was identified as one component of the IL-27R complex. To determine the functional significance of IL-27/WSX-1 during tuberculosis, we analyzed the course of infection and the immune response in WSX-1-KO mice after aerosol infection with M. tuberculosis. In the absence of WSX-I, an increased production of the proinflammatory cytokines TNF and IL-12p40 resulted in elevated CD4 + T cell activation and IFN-γ production, which enhanced macrophage effector functions and reduced bacterial loads. This is the first occasion of a selectively gene-deficient mouse strain showing higher levels of protective immunity against M. tuberculosis infection than wild-type mice. However, a concomitantly increased chronic inflammatory response also accelerated death of infected WSX-1-KO mice. In vitro, IL-27 induced STAT3 phosphorylation and inhibited TNF and IL-12 production in activated peritoneal macrophages, indicating a novel feedback mechanism by which IL-27 can modulate excessive inflammation. In conclusion, IL-27 both prevents optimal antimycobacterial protection and limits the pathological sequelae of chronic inflammation.

Bibliographical metadata

Original languageEnglish
Pages (from-to)3534-3544
Number of pages11
JournalJournal of Immunology
Volume174
Issue number6
Publication statusPublished - 15 Mar 2005