title: Chlamydia pneumoniae impairs the innate immune response in infected epithelial cells by targeting TRAF3.
abstract: Type I IFNs are induced during microbial infections and have well-characterized antiviral activities. TRAF3 is a signaling molecule crucial for type I IFN production and, therefore, represents a potential target for disarming immune responses. Chlamydia pneumoniae is a human pathogen that primarily infects respiratory epithelial cells; the onset of symptoms takes several weeks, and the course of infection is protracted. C. pneumoniae has also been associated with a variety of chronic inflammatory conditions. Thus, typical C. pneumoniae infections of humans are consistent with an impairment in inflammatory responses to the microorganism. We demonstrate that infection of epithelial cells with C. pneumoniae does not lead to IFN-β production. Instead, infected cells are prevented from activating IFN regulatory factor 3. This effect is mediated by C. pneumoniae-dependent degradation of TRAF3, which is independent of a functional proteasome. Hence, it is likely that C. pneumoniae expresses a unique protease targeting TRAF3-dependent immune effector mechanisms.
authors.affiliation: Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, FL 33136, USA. kwolf@med.miami.edu
authors.forename: Katerina
authors.initials: K
authors.lastname: Wolf
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Fields
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000276:immunology; D045744:Cell Line, Tumor; D023521:Chlamydophila Infections / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D016993:Chlamydophila pneumoniae / Q000276:immunology* / Q000472:pathogenicity; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology*; D018390:Gene Targeting; D006367:HeLa Cells; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D050838:Interferon Regulatory Factor-3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D007370:Interferon Type I / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D010766:Phosphorylation / Q000276:immunology; D020545:Respiratory Mucosa / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D048008:TNF Receptor-Associated Factor 3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; D007370:Interferon Type I; D048008:TNF Receptor-Associated Factor 3; C090656:TRAF3 protein, human