Infection of human enteroendocrine cells with Chlamydia trachomatis: a possible model for pathogenesis in irritable bowel syndrome

Neurogastroenterol Motil. 2011 Oct;23(10):928-34. doi: 10.1111/j.1365-2982.2011.01765.x. Epub 2011 Aug 21.

Abstract

Background: Irritable bowel syndrome (IBS) is a widespread gastrointestinal disorder of unknown etiology. Recently, our group detected chlamydial antigens in enteroendocrine cells (EEC) of jejunum biopsies from patients with IBS. Impairment of EEC secretion upon Chlamydia infection might lead to disturbances of gut functions. We have therefore studied the interaction between Chlamydia and EEC in vitro.

Methods: Two different human enteroendocrine cell lines were studied: LCC-18 from a neuroendocrine colonic tumour and CNDT2 from a small intestinal carcinoid. Cell lines were infected with C. trachomatis serovar LGV II strain 434. We used Penicillin G for inducing persistent infection. The ultrastructure of infected cells was studied using transmission electron microscopy and immunofluorescence and we used RT-PCR analysis for studying changes in gene expression at different stages of infection.

Key results: We found that both cell lines could be infected with C. trachomatis yielding productive infections and persistence could be induced using penicillin G. Immunofluorescence showed different cellular distributions of serotonin and chromogranin A in non-infected (cytoplasmatic distribution) compared with infected cells (serotonin and chromogranin mostly in chlamydial inclusions). In line with the microscopical findings, we found a significant down-regulation of the gene coding for the vesicular monoamine transporter (VMAT1) in infected compared with non-infected EEC (P<0.05).

Conclusions & inferences: Altered protein distributions together with down-regulation of VMAT1 suggest that chlamydial infection may influence vesicular transport. It is therefore possible that such an infection in vivo could lead to disturbances in the regulation of gut functions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Chlamydia Infections / genetics
  • Chlamydia Infections / metabolism*
  • Chlamydia trachomatis
  • Enteroendocrine Cells / metabolism
  • Enteroendocrine Cells / microbiology*
  • Fluorescent Antibody Technique
  • Gene Expression Profiling
  • Humans
  • Irritable Bowel Syndrome / genetics
  • Irritable Bowel Syndrome / metabolism*
  • Irritable Bowel Syndrome / microbiology*
  • Microscopy, Electron, Transmission
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Vesicular Monoamine Transport Proteins / biosynthesis*

Substances

  • SLC18A1 protein, human
  • Vesicular Monoamine Transport Proteins