Evasion of Innate Lymphoid Cell-Regulated Gamma Interferon Responses by Chlamydia muridarum To Achieve Long-Lasting Colonization in Mouse Colon.

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-?) 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-? 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-?, 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-? production and rescued mutant colonization. Furthermore, mice deficient in transcriptional factor ROR?t, 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-? from group 3-like ILCs.

SUBMITTER: Koprivsek JJ 

PROVIDER: S-EPMC7035925 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature