Haematopoietic innate interleukin 17A production drives immunopathology in female mouse genital Chlamydia muridarum infection.
Charles W ArmitageEmily R BryanLogan TrimElla PalframanLucas WagerKenneth W BeagleyAlison J CareyPublished in: Scandinavian journal of immunology (2024)
Chlamydia 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.
Keyphrases
- immune response
- bone marrow
- rheumatoid arthritis
- squamous cell carcinoma
- stem cells
- mouse model
- wild type
- mesenchymal stem cells
- radiation therapy
- dendritic cells
- metabolic syndrome
- deep learning
- machine learning
- cell therapy
- adipose tissue
- mass spectrometry
- interstitial lung disease
- rectal cancer
- binding protein
- atomic force microscopy
- polycystic ovary syndrome