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

Anna Zychlinsky Scharff (1) , Matthieu Rousseau (1) , Livia Lacerda Mariano (1) , Tracy Canton (1) , Camila Rosat Consiglio (1) , Matthew Albert (1) , Magnus Fontes (2, 3, 4) , Darragh Duffy (1) , Molly A Ingersoll (1)

1 Immunobiologie des Cellules dendritiques
2 IGDA - International Group for Data Analysis
3 Lund University [Lund]
4 Rigshospitalet [Copenhagen]

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.

Keywords: Sex hormones; Innate immunity; UTI/pyelonephritis; Immunology; Infectious disease

Domains: Immunology

Anna Zychlinsky Scharff, Matthieu Rousseau, Livia Lacerda Mariano, Tracy Canton, Camila Rosat Consiglio, et al.. Sex differences in IL-17 contribute to chronicity in male versus female urinary tract infection. JCI Insight, 2019, 5, ⟨10.1172/jci.insight.122998⟩. ⟨pasteur-02173511⟩