Nod1, but not the ASC inflammasome, contributes to induction of IL-1β secretion in human trophoblasts after sensing of Chlamydia trachomatis

Mucosal Immunol. 2013 Mar;6(2):235-43. doi: 10.1038/mi.2012.63. Epub 2012 Jul 4.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • CARD Signaling Adaptor Proteins
  • Carrier Proteins / metabolism
  • Cell Line
  • Chlamydia trachomatis / immunology*
  • Cytoskeletal Proteins / metabolism
  • Gene Expression
  • Humans
  • Inflammasomes / metabolism
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism*
  • Myeloid Differentiation Factor 88 / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nod1 Signaling Adaptor Protein / metabolism*
  • Toll-Like Receptor 2 / metabolism
  • Toll-Like Receptor 4 / metabolism
  • Trophoblasts / metabolism*
  • Trophoblasts / microbiology*

Substances

  • CARD Signaling Adaptor Proteins
  • Carrier Proteins
  • Cytoskeletal Proteins
  • Inflammasomes
  • Interleukin-1beta
  • Myeloid Differentiation Factor 88
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human
  • Nod1 Signaling Adaptor Protein
  • PYCARD protein, human
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4