Regulation of Chlamydia spreading from the small intestine to the large intestine via an immunological barrier

Conghui He, Ying Xu, Zhi Huo, Jie Wang, Tianjun Jia, Xiao-Dong Li, Guangming Zhong

Research output: Contribution to journalArticlepeer-review

Abstract

The obligate intracellular bacterium Chlamydia is a genital tract pathogen that can also colonize the gastrointestinal tract for long periods. The long-lasting colonization is dependent on chlamydial spreading from the small intestine to the large intestine. We previously reported that a mutant Chlamydia was able to activate an intestinal barrier for blocking its own spreading to the large intestine. In the current study, we used the mutant Chlamydia colonization model to confirm the intestinal barrier function and further to determine the immunological basis of the barrier with gene-deficient mice. Recombination activating gene 1−/− mice failed to block the mutant Chlamydia spreading, while mice deficient in toll-like receptors, myeloid differentiation primary response 88 or stimulator of interferon genes still blocked the spreading, suggesting that the intestinal barrier function is dependent on lymphocytes that express antigen receptors. Mice deficient in CD4, but not CD8 nor μ chain failed to prevent the chlamydial spreading, indicating a protective role of CD4+ cells in the intestinal barrier. Consistently, adoptive transfer of CD4+ T cells reconstituted the intestinal barrier in CD4-/- mice. More importantly, CD4+ but not CD8+ T cells nor B cells restored the intestinal barrier function in recombination activating gene 1−/− mice. Thus, CD4+ T cells are necessary and sufficient for maintaining the intestinal barrier function, indicating that the spread of an intracellular bacterium from the small intestine to the large intestine is regulated by an immunological barrier. This study has also laid a foundation for further illuminating the mechanisms by which a CD4+ T cell-dependent intestinal barrier regulates bacterial spreading in the gut.

Original languageEnglish (US)
JournalImmunology and Cell Biology
DOIs
StateAccepted/In press - 2021

Keywords

  • CD4 T cells
  • Chlamydia
  • intestinal barrier

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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