SOCS-1 protects against Chlamydia pneumoniae-induced lethal inflammation but hampers effective bacterial clearance

作者：Yang Tangbin; Stark Patrik; Janik Katrin; Wigzell Hans; Rottenberg Martin E^*

来源：The Journal of Immunology, 2008, 180(6): 4040-4049.

DOI：10.4049/jimmunol.180.6.4040

Suppressor of cytokine signaling 1 (SOCS1) plays a major role in the inhibition of STAT1-mediated responses. STAT1-dependent responses are critical for resistance against infection with Chlamydia pneumoniae. We studied the regulation of expression of SOCS1 and SOCS3, and the role of SOCS1 during infection with C. pneumoniae in mice. Bone marrow-derived macrophages (BMM) and dendritic cells in vitro or lungs in vivo all showed enhanced STAT1-dependent SOCS1 mRNA accumulation after infection with C. pneumoniae. Infection-increased SOCS1 mRNA levels were dependent on IFN-alpha beta but not on IFN-gamma.. T or B cells were not required for SOCS1 mRNA accumulation in vivo. Infection-induced STAT1-phosphorylation occurred more rapidly in SOCS1(-/-) BMM. In agreement, expression of IFN-gamma responsive genes, but not IL-1 beta, IL-6, or TNF-alpha were relatively increased in C. pneumoniae-infected SOCS1(-/-) BMM. Surprisingly, C. pneumoniae infection-induced IFN-alpha, IFN-beta, and IFN-gamma expression in BMM were attenuated by SOCS1. C. pneumoniae infection of RAG1(-/-)/SOCS1(-/-) mice induced a rapid lethal inflammation, accompanied by diminished pulmonary bacterial load and increased levels of NOS and IDO but not IL-1 beta, IL-6, or TNF-a mRNA. In summary, C pneumoniae infection induces a STAT1, IFN-alpha beta-dependent and IFN-gamma independent SOCS1 mRNA accumulation. Presence of SOCSI controls the infection-induced lethal inflammatory disease but impairs the bacterial control.

• 出版日期2008-3-15
• 单位中国航天员科研训练中心