title: Nod1-mediated endothelial cell activation by Chlamydophila pneumoniae.
abstract: Seroepidemiological and animal studies, as well as demonstration of viable bacteria in atherosclerotic plaques, have linked Chlamydophila pneumoniae infection to development of chronic vascular lesions and coronary heart disease. Inflammation and immune responses are dependent on host recognition of invading pathogens. The recently identified cytosolic Nod proteins are candidates for intracellular recognition of bacteria, such as the obligate intracellular chlamydia. In the present study, mechanisms of endothelial cell activation by C. pneumoniae via Nod proteins were examined. Viable, but not heat-inactivated, chlamydia activated human endothelial cells, suggesting that invasion of these cells is necessary for their profound activation. Endothelial cells express Nod1. Nod1 gene silencing by small interfering RNA reduced C pneumoniae-induced IL-8 release markedly. Moreover, in HEK293 cells, overexpressed Nod1 or Nod2 amplified the capacity of C pneumoniae to induce nuclear factor kappaB (NF-kappaB) activation. Interestingly, heat-inactivated bacteria were still able to induced a NF-kappaB reporter gene activity via Nod proteins when transfected intracellularly, but not when provided from the extracellular side. In contrast, TLR2 sensed extracellular heat-inactivated chlamydia. In conclusion, we demonstrated that C pneumoniae induced a Nod1-mediated and Nod2-mediated NF-kappaB activation in HEK293 cells. In endothelial cells, Nod1 played a dominant role in triggering a chlamydia-mediated inflammatory process.
authors.affiliation: Department of Internal Medicine/Infectious Diseases, Charité University Medicine Berlin, Berlin, Germany.
authors.forename: Bastian
authors.initials: B
authors.lastname: Opitz
authors.forename: Stefanie
authors.initials: S
authors.lastname: Förster
authors.forename: Andreas C
authors.initials: AC
authors.lastname: Hocke
authors.forename: Matthias
authors.initials: M
authors.lastname: Maass
authors.forename: Bernd
authors.initials: B
authors.lastname: Schmeck
authors.forename: Stefan
authors.initials: S
authors.lastname: Hippenstiel
authors.forename: Norbert
authors.initials: N
authors.lastname: Suttorp
authors.forename: Matthias
authors.initials: M
authors.lastname: Krüll
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000502:physiology*; D000943:Antigens, Differentiation / Q000378:metabolism; D001011:Aorta / Q000166:cytology; D002460:Cell Line; D016993:Chlamydophila pneumoniae / Q000276:immunology* / Q000502:physiology; D042783:Endothelial Cells / Q000378:metabolism / Q000382:microbiology* / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology; D005110:Extracellular Space / Q000382:microbiology; D005786:Gene Expression Regulation / Q000502:physiology*; D020868:Gene Silencing / Q000502:physiology; D006358:Hot Temperature; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology; D042541:Intracellular Space / Q000382:microbiology; D007668:Kidney / Q000196:embryology / Q000382:microbiology; D008562:Membrane Glycoproteins / Q000502:physiology; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B / Q000502:physiology; D053474:Nod1 Signaling Adaptor Protein; D053473:Nod2 Signaling Adaptor Protein; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D034741:RNA, Small Interfering / Q000502:physiology; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2; D011956:Receptors, Cell Surface / Q000502:physiology; D011971:Receptors, Immunologic / Q000378:metabolism; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D014471:Umbilical Veins / Q000166:cytology; D015164:Vaccines, Inactivated / Q000276:immunology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; D016209:Interleukin-8; D047908:Intracellular Signaling Peptides and Proteins; C507779:MYD88 protein, human; D008562:Membrane Glycoproteins; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; C119067:NOD1 protein, human; C429018:NOD2 protein, human; D053474:Nod1 Signaling Adaptor Protein; D053473:Nod2 Signaling Adaptor Protein; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D015164:Vaccines, Inactivated; D017346:Protein Serine-Threonine Kinases; C506253:RIPK2 protein, human; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2