Silencing suppressor of cytokine signaling-1 (SOCS1) in macrophages improves Mycobacterium tuberculosis control in an interferon-γ (IFN-γ)-dependent manner

Berit Carow, Xiang Qun Ye, Dolores Gavier-Wide, Sabin Bhuju, Wulf Oehlmann, Mahavir Singh, Markus Sköld, Lech Ignatowicz, Akihiko Yoshimura, Hans Wigzell, Martin E. Rottenberg

研究成果: Article査読

37 被引用数 (Scopus)

抄録

Protection against infection with Mycobacterium tuberculosis demands IFN-γ. SOCS1 has been shown to inhibit responses to IFN-γ and might thereby play a central role in the outcome of infection. We found that M. tuberculosis is a highly efficient stimulator of SOCS1 expression in murine and human macrophages and in tissues from infected mice. Surprisingly, SOCS1 reduced responses to IL-12, resulting in an impaired IFN-γ secretion by macrophages that in turn accounted for a deteriorated intracellular mycobacterial control. Despite SOCS1 expression, mycobacteria-infected macrophages responded to exogenously added IFN-γ. SOCS1 attenuated the expression of the majority of genes modulated by M. tuberculosis infection of macrophages. Using a conditional knockdown strategy in mice, we found that SOCS1 expression by macrophages hampered M. tuberculosis clearance early after infection in vivo in an IFN-γ-dependent manner. On the other hand, at later time points, SOCS1 expression by non-macrophage cells protected the host from infection-induced detrimental inflammation.

本文言語English
ページ(範囲)26873-26887
ページ数15
ジャーナルJournal of Biological Chemistry
286
30
DOI
出版ステータスPublished - 2011 7 29

ASJC Scopus subject areas

  • 生化学
  • 分子生物学
  • 細胞生物学

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