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Forskningsartikel2011Vetenskapligt granskadÖppen tillgång

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.

Publicerad i

Journal of Biological Chemistry
2011, Volym: 286, nummer: 30, sidor: 26873-26887

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    Biokemi och molekylärbiologi

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