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Research article - Peer-reviewed, 2011

Silencing Suppressor of Cytokine Signaling-1 (SOCS1) in Macrophages Improves Mycobacterium tuberculosis Control in an Interferon-gamma (IFN-gamma)-dependent Manner

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


Protection against infection with Mycobacterium tuberculosis demands IFN-gamma. SOCS1 has been shown to inhibit responses to IFN-gamma 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-gamma secretion by macrophages that in turn accounted for a deteriorated intracellular mycobacterial control. Despite SOCS1 expression, mycobacteria-infected macrophages responded to exogenously added IFN-gamma. 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-gamma -dependent manner. On the other hand, at later time points, SOCS1 expression by non-macrophage cells protected the host from infection-induced detrimental inflammation.

Published in

Journal of Biological Chemistry
2011, volume: 286, number: 30, pages: 26873-26887

Authors' information

Carow, Berit
Ye, Xiang qun
Gavier-Widen, Dolores (Gavier Widén, Dolores)
Swedish University of Agricultural Sciences, Department of Biomedical Science and Veterinary Public Health
Bhuju, Sabin
Oehlmann, Wulf
Singh, Mahavir
Sköld, Markus
Ignatowicz, Lech
Yoshimura, Akihiko
Wigzell, Hans
Rottenberg, Martin E.

Sustainable Development Goals

SDG3 Good health and well-being

UKÄ Subject classification

Biochemistry and Molecular Biology

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