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Induction of iNOS by Chlamydophila pneumoniae requires MyD88‐dependent activation of JNK
Author(s) -
Rodriguez Nuria,
Lang Roland,
Wantia Nina,
Cirl Christine,
Ertl Tanja,
Dürr Susanne,
Wagner Hermann,
Miethke Thomas
Publication year - 2008
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0508304
Subject(s) - chlamydophila pneumoniae , biology , stat1 , innate immune system , phosphorylation , nitric oxide synthase , transcription factor , irf1 , nf κb , immune system , tumor necrosis factor alpha , signal transduction , microbiology and biotechnology , nfkb1 , stat3 , immunology , nitric oxide , chlamydiales , gene , chlamydia , biochemistry , endocrinology
Innate immune cells produce NO via inducible NO synthase (iNOS) in response to certain infections or upon stimulation with cytokines such as IFN‐γ and TNF. NO plays an important role in host defense against intracellular bacteria including Chlamydophila pneumoniae as a result of its microbicidal activity. In MyD88‐deficient mice, which succumb to C. pneumoniae infection, iNOS induction is impaired 6 days postinfection, although pulmonary levels of IFN‐γ and TNF are elevated as in wild‐type mice at this time‐point. Here, we demonstrate that induction of iNOS in macrophages upon C. pneumoniae infection is controlled by MyD88 via two pathways: NF‐κB activation and phosphorylation of the MAPK JNK, which leads to the nuclear translocation of c‐Jun, one of the two components of the AP‐1 complex. In addition, phosphorylation of STAT1 and expression of IFN regulatory factor 1 (IRF‐1) were delayed in the absence of MyD88 after C. pneumoniae infection but not after IFN‐γ stimulation. Taken together, our data show that for optimal induction of iNOS during C. pneumoniae infection, the concerted action of the MyD88‐dependent transcription factors NF‐κB and AP‐1 and of the MyD88‐independent transcription factors phosphorylated STAT1 and IRF‐1 is required.