Publication Date:
2017-08-01
Description:
GenitalChlamydia trachomatisinfections in women typically are asymptomatic and do not cause permanent upper genital tract (UGT) damage. Consistent with this presentation, type 2 innate and TH2 adaptive immune responses associated with dampened inflammation and tissue repair are elicited in the UGT ofChlamydia-infected women. PrimaryC. trachomatisinfection of mice also causes no genital pathology, but unlike women, does not generateChlamydia-specific TH2 immunity. Herein, we explored the significance of type 2 innate immunity for restricting UGT tissue damage inChlamydia-infected mice, and in initial studies intravaginally infected wild-type, IL-10−/−, IL-4−/−, and IL-4Rα−/−mice with low-doseC. trachomatisinoculums. WhereasChlamydiawas comparably cleared in all groups, IL-4−/−and IL-4Rα−/−mice displayed endometrial damage not seen in wild-type or IL-10−/−mice. Congruent with the aberrant tissue repair in mice with deficient IL-4 signaling, we found that IL-4Rα and STAT6 signaling mediated IL-4–induced endometrial stromal cell (ESC) proliferation ex vivo, and that genital administration of an IL-4–expressing adenoviral vector greatly increased in vivo ESC proliferation. Studies with IL-4-IRES-eGFP (4get) reporter mice showed eosinophils were the main IL-4–producing endometrial leukocyte (constitutively and duringChlamydiainfection), whereas studies with eosinophil-deficient mice identified this innate immune cell as essential for endometrial repair duringChlamydiainfection. Together, our studies reveal IL-4–producing eosinophils stimulate ESC proliferation and preventChlamydia-induced endometrial damage. Based on these results, it seems possible that the robust type 2 immunity elicited byChlamydiainfection of human genital tissue may analogously promote repair processes that reduce phenotypic disease expression.
Print ISSN:
0027-8424
Electronic ISSN:
1091-6490
Topics:
Biology
,
Medicine
,
Natural Sciences in General
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