Gavier Widén, Dolores
- Department of Animal Biosciences, Swedish University of Agricultural Sciences
Research article2011Peer reviewedOpen access
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.
Journal of Biological Chemistry
2011, Volume: 286, number: 30, pages: 26873-26887
Publisher: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Ensure healthy lives and promote well-being for all at all ages
Biochemistry and Molecular Biology
DOI: https://doi.org/10.1074/jbc.M111.238287
https://res.slu.se/id/publ/46507