Published online before print September 17, 2008
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Institut für Medizinische Mikrobiologie, Immunologie und Hygiene, Technische Universität München, München, Germany
1 Correspondence: Institute of Medical Microbiology, Immunology and Hygiene, Technical University of Munich, Trogerstr. 30, 81675 Munich, Germany. E-mail: thomas.miethke{at}lrz.tum.de
Innate immune cells produce NO via inducible NO synthase (iNOS) in response to certain infections or upon stimulation with cytokines such as IFN-
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- 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-
B 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- 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-B and AP-1 and of the MyD88-independent transcription factors phosphorylated STAT1 and IRF-1 is required.
Key Words: bacterial infection • immune response • IFN- • Toll-like receptors • MAPK
