Characterization of apoptotic activities during chlamydia trachomatis infection in primary cervical epithelial cells

Immunol Invest. 2010;39(7):674-87. doi: 10.3109/08820139.2010.485626.

Abstract

Chlamydiae are obligate intracellular bacteria that infect human epithelial cells. It has been reported that Chlamydia trachomatis, induces apoptosis in epithelial cells, however, the molecular mechanisms responsible for host cell death especially in primary epithelial cells remained largely unknown as most of the studies are in cell line like HeLa. In this study we demonstrated that C. trachomatis induces apoptosis signaling pathway and apoptosis in primary cervical epithelial cells in a time and dose dependent manner. Live cervical epithelial cells were isolated from endocervical cells and induction was done with chlamydial EBs. Our results demonstrated that apoptosis in infected epithelial cells was associated with an increased activity of caspase 8; however, caspase 9 was activated to a lesser extent. Analysis of apoptosis pathway revealed that expression level of McL-1, Bcl-2, CASP8, and TRADD genes were found to be significantly upregulated (P < 0.01), where as levels of Caspase 1, Caspase 10 and BRIC2 were found to be significantly downregulated (p < 0.01). Our results showed that Chlamydia induces apoptosis and caspase activation in epithelial cells through caspase 8, with an increased expression of the McL-1, which confers a block at the mitochondrial level.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / immunology
  • Caspase 8 / genetics
  • Caspase 8 / metabolism*
  • Cell Culture Techniques
  • Cells, Cultured
  • Cervix Uteri / pathology
  • Chlamydia Infections / immunology*
  • Chlamydia Infections / pathology
  • Chlamydia trachomatis / immunology*
  • Chlamydia trachomatis / pathogenicity
  • Enzyme Activation / immunology
  • Epithelial Cells / immunology
  • Epithelial Cells / metabolism*
  • Epithelial Cells / pathology
  • Female
  • Gene Expression Regulation / immunology
  • Humans
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Signal Transduction / immunology

Substances

  • Myeloid Cell Leukemia Sequence 1 Protein
  • Proto-Oncogene Proteins c-bcl-2
  • Caspase 8