title: Nod1, but not the ASC inflammasome, contributes to induction of IL-1β secretion in human trophoblasts after sensing of Chlamydia trachomatis.
abstract: Chlamydia trachomatis (Ct) is an obligate intracellular bacterial pathogen. Previously, we showed that infection of human trophoblast cells by Ct triggers the secretion of the pro-inflammatory cytokine, interleukin (IL)-1β. The aim of this study was to understand the innate immune pathways involved in trophoblast production of IL-1β after Ct infection. The approach we took was to inhibit the expression or function of the key Toll-like receptors (TLRs), Nod-like receptors, and inflammasome components that have been associated with chlamydia infection. In this study, we report that Ct-induced trophoblast IL-1β secretion is associated with the transcription of IL-1β mRNA, the translation and processing of pro-IL-1β, and the activation of caspase-1. In addition, we demonstrate that Ct-induced IL-1β production and secretion by the trophoblast is independent of TLR2, TLR4, MyD88, and the Nalp3/ASC inflammasome. Instead we report, for the first time, the importance of Nod1 for mediating trophoblast IL-1β secretion in response to a Ct infection.
authors: Department of Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut, USA. paula.kavathas@yale.edu
authors: P B
authors: PB
authors: Kavathas
authors: C M
authors: CM
authors: Boeras
authors: M J
authors: MJ
authors: Mulla
authors: V M
authors: VM
authors: Abrahams
mesh_terms: D053468:CARD Signaling Adaptor Proteins; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D002692:Chlamydia trachomatis / Q000276:immunology*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism*; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D053474:Nod1 Signaling Adaptor Protein / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014327:Trophoblasts / Q000378:metabolism* / Q000382:microbiology*
chemical_list: D053468:CARD Signaling Adaptor Proteins; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D058847:Inflammasomes; D053583:Interleukin-1beta; D053594:Myeloid Differentiation Factor 88; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D053474:Nod1 Signaling Adaptor Protein; C402202:PYCARD protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4