Abstract
AbstractThe human pathogen Neisseria gonorrhoeae ascends into the upper female reproductive tract to cause damaging inflammation within the Fallopian tubes and pelvic inflammatory disease (PID), increasing the risk of infertility and ectopic pregnancy. The loss of ciliated cells from the epithelium is thought to be both a consequence of inflammation and a cause of adverse sequelae. However, the links between infection, inflammation, and ciliated cell extrusion remain unresolved. With the use of ex vivo cultures of human Fallopian tube paired with RNA sequencing we defined the tissue response to gonococcal challenge, identifying cytokine, chemokine, cell adhesion, and apoptosis related transcripts not previously recognized as potentiators of gonococcal PID. Unexpectedly, IL-17C was one of the most highly induced genes. Yet, this cytokine has no previous association with gonococcal infection nor pelvic inflammatory disease and thus it was selected for further characterization. We show that human Fallopian tubes express the IL-17C receptor on the epithelial surface and that treatment with purified IL-17C induces pro-inflammatory cytokine secretion in addition to sloughing of the epithelium and generalized tissue damage. These results demonstrate a previously unrecognized but critical role of IL-17C in the damaging inflammation induced by gonococci in a human explant model of PID.
Funder
U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases
Publisher
Springer Science and Business Media LLC
Reference133 articles.
1. Platt, R., Rice, P. A. & McCormack, W. M. Risk of acquiring gonorrhea and prevalence of abnormal adnexal findings among women recently exposed to gonorrhea. JAMA 250, 3205–3209 (1983).
2. Lovett, A. & Duncan, J. A. Human immune responses and the natural history of Neisseria gonorrhoeae infection. Front Immunol. 9, 3187 (2018).
3. Haggerty, C. L., Hillier, S. L., Bass, D. C. & Ness, R. B. Bacterial vaginosis and anaerobic bacteria are associated with endometritis. Clin. Infect. Dis. 39, 990–995 (2004).
4. Eschenbach, D. A. et al. Polymicrobial etiology of acute pelvic inflammatory disease. N. Engl. J. Med. 293, 166–171 (1975).
5. Sweet, R. L., Draper, D. L. & Hadley, W. K. Etiology of acute salpingitis: influence of episode number and duration of symptoms. Obstet. Gynecol. 58, 62–68 (1981).
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