Sex differences in IL-17 contribute to chronicity in male versus female urinary tract infection
(2019) In JCI Insight 4(13).- Abstract
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... (More)
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.
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- author
- Scharff, Anna Zychlinsky ; Rousseau, Matthieu ; Mariano, Livia Lacerda ; Canton, Tracy ; Consiglio, Camila Rosat ; Albert, Matthew L. ; Fontes, Magnus LU ; Duffy, Darragh and Ingersoll, Molly A.
- organization
- publishing date
- 2019-07-11
- type
- Contribution to journal
- publication status
- published
- subject
- in
- JCI Insight
- volume
- 4
- issue
- 13
- article number
- e122998
- publisher
- The American Society for Clinical Investigation
- external identifiers
-
- scopus:85070660565
- pmid:31145099
- ISSN
- 2379-3708
- DOI
- 10.1172/jci.insight.122998
- language
- English
- LU publication?
- yes
- id
- aa0e277f-9de8-4ea6-b035-30e4bb6a79c2
- date added to LUP
- 2019-08-30 10:11:01
- date last changed
- 2024-05-14 20:51:56
@article{aa0e277f-9de8-4ea6-b035-30e4bb6a79c2,
abstract = {{<p>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.</p>}},
author = {{Scharff, Anna Zychlinsky and Rousseau, Matthieu and Mariano, Livia Lacerda and Canton, Tracy and Consiglio, Camila Rosat and Albert, Matthew L. and Fontes, Magnus and Duffy, Darragh and Ingersoll, Molly A.}},
issn = {{2379-3708}},
language = {{eng}},
month = {{07}},
number = {{13}},
publisher = {{The American Society for Clinical Investigation}},
series = {{JCI Insight}},
title = {{Sex differences in IL-17 contribute to chronicity in male versus female urinary tract infection}},
url = {{http://dx.doi.org/10.1172/jci.insight.122998}},
doi = {{10.1172/jci.insight.122998}},
volume = {{4}},
year = {{2019}},
}