Haematopoietic innate interleukin 17A production drives immunopathology in female mouse genital Chlamydia muridarum infection

Author:

Armitage Charles W.12,Bryan Emily R.1ORCID,Trim Logan1,Palframan Ella1,Wager Lucas1,Beagley Kenneth W.1,Carey Alison J.1ORCID

Affiliation:

1. School of Biomedical Science and Centre for Immunology and Infection Control, Faculty of Health Queensland University of Technology Brisbane Queensland Australia

2. Peter Goher Department of Immunobiology Kings College London London UK

Abstract

AbstractChlamydia trachomatis infection is the leading cause of bacterial urogenital infection and has been demonstrated to drive inflammation and scarring of the reproductive tract. Recent studies have identified key triggers of proinflammatory adaptive immune responses driven by innate leukocytes and epithelia driving immunopathology. Utilizing chimeric mouse models, we investigated the definitive source and role of IL17 and IL17 signalling receptors during early Chlamydia muridarum infection of the female urogenital tract. Bone marrow transplants from wild‐type (WT) and IL17A−/− mice to recipients demonstrated equivocal infection kinetics in the reproductive tract, but interestingly, adoptive transfer of IL17A−/− immune cells to WT recipients resulted in no infertility, suggesting a haematopoietic (as opposed to tissue) source of IL17 driving immunopathology. To further delineate the role of IL17 in immunopathology, we infected WT and IL17 receptor A (IL17RA)−/− female mice and observed a significant reduction in immunopathology in IL17RA−/− mice. WT bone marrow transplants to IL17RA−/− recipient mice prevented hydrosalpinx, suggesting signalling through IL17RA drives immunopathology. Furthermore, early chemical inhibition of IL17 signalling significantly reduced hydrosalpinx, suggesting IL17 acts as an innate driver of disease. Early during the infection, IL17 was produced by γδ T cells in the cervico‐vagina, but more importantly, by neutrophils at the site of infertility in the oviducts. Taken together, these data suggest innate production of IL17 by haematopoietic leukocytes drives immunopathology in the epithelia during early C. muridarum infection of the female reproductive tract.

Funder

National Health and Medical Research Council

Publisher

Wiley

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