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* Department of Microbiology, Tumorbiology and Cell Biology, Karolinska Institute, Stockholm, Sweden;
Laboratory of Space Cellular and Molecular Biology, China Astronaut Research and Training Center, Beijing, China; and
Department of Medical Microbiology, Medical School Hannover, Hanover, Germany
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-
β but not on IFN-
. 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- responsive genes, but not IL-1β, IL-6, or TNF- were relatively increased in C. pneumoniae-infected SOCS1–/– BMM. Surprisingly, C. pneumoniae infection-induced IFN-, IFN-β, and IFN- 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 iNOS and IDO but not IL-1β, IL-6, or TNF- mRNA. In summary, C. pneumoniae infection induces a STAT1, IFN-β-dependent and IFN- independent SOCS1 mRNA accumulation. Presence of SOCS1 controls the infection-induced lethal inflammatory disease but impairs the bacterial control.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by the European Community QLK2-CT-2002-00846 grant, the Karolinska Institute, and by the International Research Training Group 1273, funded by the German Research Foundation and the Swedish Research Council.
2 Address correspondence and reprint requests to Dr. Martin E. Rottenberg, Department of Microbiology, Tumorbiology and Cell Biology, Karolinska Institute, 171 77 Stockholm, Sweden. E-mail address: Martin.Rottenberg{at}ki.se
3 Abbreviations used in this paper: SOCS, suppressor of cytokine signaling; BMM, bone marrow-derived macrophage; BMDC, bone marrow-derived dendritic cell; WT, wild type.
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