Stimulation of the cytosolic receptor for peptidoglycan, Nod1, by infection with Chlamydia trachomatis or Chlamydia muridarum

Cell Microbiol. 2006 Jun;8(6):1047-57. doi: 10.1111/j.1462-5822.2006.00686.x.

Abstract

Infection of epithelial cells by the intracellular pathogen, Chlamydia trachomatis, leads to activation of NF-kappaB and secretion of pro-inflammatory cytokines. We find that overexpression of a dominant-negative Nod1 or depletion of Nod1 by RNA interference inhibits partially the activation of NF-kappaB during chlamydial infection in vitro, suggesting that Nod1 can detect the presence of Chlamydia. In parallel, there is a larger increase in the expression of pro-inflammatory genes following Chlamydia infection when primary fibroblasts are isolated from wild-type mice than from Nod1-deficient mice. The Chlamydia genome encodes all the putative enzymes required for proteoglycan synthesis, but proteoglycan from Chlamydia has never been detected biochemically. Since Nod1 is a ubiquitous cytosolic receptor for peptidoglycan from Gram-negative bacteria, our results suggest that C. trachomatis and C. muridarum do in fact produce at least the rudimentary proteoglycan motif recognized by Nod1. Nonetheless, Nod1 deficiency has no effect on the efficiency of infection, the intensity of cytokine secretion, or pathology in vaginally infected mice, compared with wild-type controls. Similarly, Rip2, a downstream mediator of Nod1, Toll-like receptor (TLR)-2, and TLR4, increases only slightly the intensity of chlamydial infection in vivo and has a very mild effect on the immune response and pathology. Thus, Chlamydia may not produce sufficient peptidoglycan to stimulate Nod1-dependent pathways efficiently in infected animals, or other receptors of the innate immune system may compensate for the absence of Nod1 during Chlamydia infection in vivo.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / physiology*
  • Animals
  • Chlamydia Infections / pathology
  • Chlamydia Infections / physiopathology*
  • Chlamydia muridarum / chemistry
  • Chlamydia muridarum / pathogenicity*
  • Chlamydia muridarum / physiology*
  • Chlamydia trachomatis / chemistry
  • Chlamydia trachomatis / pathogenicity*
  • Chlamydia trachomatis / physiology*
  • DNA, Bacterial / analysis
  • DNA, Bacterial / genetics
  • Epithelium / chemistry
  • Epithelium / microbiology
  • Epithelium / pathology
  • Epithelium / physiology
  • Female
  • Fibroblasts / microbiology
  • Fibroblasts / physiology
  • Gene Expression Regulation, Bacterial / physiology
  • HeLa Cells
  • Humans
  • Male
  • Mice
  • Mice, Inbred NOD
  • NF-kappa B / analysis
  • NF-kappa B / physiology
  • Nod1 Signaling Adaptor Protein
  • Protein Serine-Threonine Kinases / physiology
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics
  • Receptor-Interacting Protein Serine-Threonine Kinase 2
  • Receptor-Interacting Protein Serine-Threonine Kinases
  • Receptors, Cell Surface / analysis
  • Receptors, Cell Surface / physiology*
  • Toll-Like Receptor 2 / genetics
  • Toll-Like Receptor 2 / physiology
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / physiology
  • Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / physiology
  • Vagina / microbiology

Substances

  • Adaptor Proteins, Signal Transducing
  • DNA, Bacterial
  • NF-kappa B
  • Nod1 Signaling Adaptor Protein
  • Nod1 protein, mouse
  • RNA, Messenger
  • Receptors, Cell Surface
  • Tlr2 protein, mouse
  • Tlr4 protein, mouse
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
  • Protein Serine-Threonine Kinases
  • RIPK2 protein, human
  • Receptor-Interacting Protein Serine-Threonine Kinase 2
  • Receptor-Interacting Protein Serine-Threonine Kinases
  • Ripk2 protein, mouse