Sex differences in IL-17 contribute to chronicity in male versus female urinary tract infection.

Zychlinsky Scharff A, Rousseau M, Lacerda Mariano L, Canton T, Consiglio CR, Albert ML, Fontes M, Duffy D, Ingersoll MA

JCI Insight 5 (13) - [2019-05-30; online 2019-05-30]

Sex-based differences influence incidence and outcome of infectious disease. Women have a significantly greater incidence of urinary tract infection (UTI) than men, yet, conversely, male UTI is more persistent with greater associated morbidity. Mechanisms underlying these sex-based differences are unknown, in part due to a lack of experimental models. We optimized a model to transurethrally infect male mice and directly compared UTI in both sexes. Although both sexes were initially equally colonized by uropathogenic E. coli, only male and testosterone-treated female mice remained chronically infected for up to 4 weeks. Female mice had more robust innate responses, including higher IL-17 expression, and increased γδ T cells and group 3 innate lymphoid cells in the bladder following infection. Accordingly, neutralizing IL-17 abolished resolution in female mice, identifying a cytokine pathway necessary for bacterial clearance. Our findings support the concept that sex-based responses to UTI contribute to impaired innate immunity in males and provide a rationale for non-antibiotic-based immune targeting to improve the response to UTI.

Camila Consiglio

DDLS Fellow

PubMed 31145099

DOI 10.1172/jci.insight.122998

Crossref 10.1172/jci.insight.122998

pmc: PMC6629110
pii: 122998

Publications 9.5.0