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

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)26873-26887
Number of pages15
JournalJournal of Biological Chemistry
Volume286
Issue number30
DOIs
Publication statusPublished - 2011 Jul 29

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Macrophages
Mycobacterium tuberculosis
Interferons
Cytokines
Infection
Mycobacterium Infections
Interleukin-12
Mycobacterium
Genes
Tissue
Inflammation
Gene Expression

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Silencing suppressor of cytokine signaling-1 (SOCS1) in macrophages improves Mycobacterium tuberculosis control in an interferon-γ (IFN-γ)-dependent manner. / Carow, Berit; Ye, Xiang Qun; Gavier-Wide, Dolores; Bhuju, Sabin; Oehlmann, Wulf; Singh, Mahavir; Sköld, Markus; Ignatowicz, Lech; Yoshimura, Akihiko; Wigzell, Hans; Rottenberg, Martin E.

In: Journal of Biological Chemistry, Vol. 286, No. 30, 29.07.2011, p. 26873-26887.

Research output: Contribution to journalArticle

Carow, B, Ye, XQ, Gavier-Wide, D, Bhuju, S, Oehlmann, W, Singh, M, Sköld, M, Ignatowicz, L, Yoshimura, A, Wigzell, H & Rottenberg, ME 2011, 'Silencing suppressor of cytokine signaling-1 (SOCS1) in macrophages improves Mycobacterium tuberculosis control in an interferon-γ (IFN-γ)-dependent manner', Journal of Biological Chemistry, vol. 286, no. 30, pp. 26873-26887. https://doi.org/10.1074/jbc.M111.238287
Carow, Berit ; Ye, Xiang Qun ; Gavier-Wide, Dolores ; Bhuju, Sabin ; Oehlmann, Wulf ; Singh, Mahavir ; Sköld, Markus ; Ignatowicz, Lech ; Yoshimura, Akihiko ; Wigzell, Hans ; Rottenberg, Martin E. / Silencing suppressor of cytokine signaling-1 (SOCS1) in macrophages improves Mycobacterium tuberculosis control in an interferon-γ (IFN-γ)-dependent manner. In: Journal of Biological Chemistry. 2011 ; Vol. 286, No. 30. pp. 26873-26887.
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