| First Author | Vicetti Miguel RD | Year | 2017 |
| Journal | Proc Natl Acad Sci U S A | Volume | 114 |
| Issue | 33 | Pages | E6892-E6901 |
| PubMed ID | 28765368 | Mgi Jnum | J:243776 |
| Mgi Id | MGI:5912555 | Doi | 10.1073/pnas.1621253114 |
| Citation | Vicetti Miguel RD, et al. (2017) IL-4-secreting eosinophils promote endometrial stromal cell proliferation and prevent Chlamydia-induced upper genital tract damage. Proc Natl Acad Sci U S A 114(33):E6892-E6901 |
| abstractText | Genital Chlamydia trachomatis infections 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 of Chlamydia-infected women. Primary C. trachomatis infection of mice also causes no genital pathology, but unlike women, does not generate Chlamydia-specific TH2 immunity. Herein, we explored the significance of type 2 innate immunity for restricting UGT tissue damage in Chlamydia-infected mice, and in initial studies intravaginally infected wild-type, IL-10-/-, IL-4-/-, and IL-4Ralpha-/- mice with low-dose C. trachomatis inoculums. Whereas Chlamydia was comparably cleared in all groups, IL-4-/- and IL-4Ralpha-/- 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-4Ralpha 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 during Chlamydia infection), whereas studies with eosinophil-deficient mice identified this innate immune cell as essential for endometrial repair during Chlamydia infection. Together, our studies reveal IL-4-producing eosinophils stimulate ESC proliferation and prevent Chlamydia-induced endometrial damage. Based on these results, it seems possible that the robust type 2 immunity elicited by Chlamydia infection of human genital tissue may analogously promote repair processes that reduce phenotypic disease expression. |
