| First Author | Carow B | Year | 2011 |
| Journal | J Biol Chem | Volume | 286 |
| Issue | 30 | Pages | 26873-87 |
| PubMed ID | 21622562 | Mgi Jnum | J:175389 |
| Mgi Id | MGI:5285473 | Doi | 10.1074/jbc.M111.238287 |
| Citation | Carow B, et al. (2011) Silencing suppressor of cytokine signaling-1 (SOCS1) in macrophages improves Mycobacterium tuberculosis control in an interferon-gamma (IFN-gamma)-dependent manner. J Biol Chem 286(30):26873-87 |
| abstractText | 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. |
