Evasion of innate lymphoid cell-regulated gamma interferon responses by chlamydia muridarum to achieve long-lasting colonization in mouse colon

John J. Koprivsek, Ying He, Chenchen Song, Nu Zhang, Alexei Tumanov, Guangming Zhong

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Revealing the mechanisms by which bacteria establish long-lasting colonization in the gastrointestinal tract is an area of intensive investigation. The obligate intracellular bacterium Chlamydia is known to colonize mouse colon for long periods. A colonization-deficient mutant strain of this intracellular bacterium is able to regain long-lasting colonization in gamma interferon (IFN-γ) knockout mice following intracolon inoculation. We now report that mice deficient in conventional T lymphocytes or recombination-activating gene (Rag) failed to show rescue of mutant colonization. Nevertheless, antibody depletion of IFN-γ or genetic deletion of interleukin 2 (IL-2) receptor common gamma chain in Rag-deficient mice did rescue mutant colonization. These observations suggest that colonic IFN-γ, responsible for inhibiting the intracellular bacterial mutant, is produced by innate lymphoid cells (ILCs). Consistently, depletion of NK1.1+ cells in Rag-deficient mice both prevented IFN-γ production and rescued mutant colonization. Furthermore, mice deficient in transcriptional factor RORγt, but not chemokine receptor CCR6, showed full rescue of the long-lasting colonization of the mutant, indicating a role for group 3-like ILCs. However, the inhibitory function of the responsible group 3-like ILCs was not dependent on the natural killer cell receptor (NCR1), since NCR1-deficient mice still inhibited mutant colonization. Consistently, mice deficient in the transcriptional factor T-bet only delayed the clearance of the bacterial mutant without fully rescuing the long-lasting colonization of the mutant. Thus, we have demonstrated that the obligate intracellular bacterium Chlamydia maintains its long-lasting colonization in the colon by evading IFN-γ from group 3-like ILCs.

Original languageEnglish (US)
Article numbere00798-19
JournalInfection and immunity
Volume88
Issue number3
DOIs
StatePublished - Mar 1 2020

Keywords

  • Chlamydia
  • IFN-γ
  • Innate lymphoid cells
  • Obligate intracellular pathogen
  • RORγt

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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