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

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

SUBMITTER: Carow B 

PROVIDER: S-EPMC3143647 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature