Evasion of innate lymphoid cells-regulated IFNγ responses by Chlamydia muridarum to achieve long-lasting colonization in mouse colon.
2019
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-gamma) 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-gamma 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-gamma, 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-gamma production and rescued mutant colonization. Furthermore, mice deficient in transcriptional factor RORgammat, 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-gamma from group 3-like ILCs.
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