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Lactobacillus crispatus Limits Bladder Uropathogenic E. coli Infection by Triggering a Host Type I Interferon Response.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2022 Aug 16; Vol. 119 (33), pp. e2117904119. Date of Electronic Publication: 2022 Aug 08. - Publication Year :
- 2022
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Abstract
- Many urinary tract infections (UTIs) are recurrent because uropathogens persist within the bladder epithelial cells (BECs) for extended periods between bouts of infection. Because persistent uropathogens are intracellular, they are often refractive to antibiotic treatment. The recent discovery of endogenous Lactobacillus spp. in the bladders of healthy humans raised the question of whether these endogenous bacteria directly or indirectly impact intracellular bacterial burden in the bladder. Here, we report that in contrast to healthy women, female patients experiencing recurrent UTIs have a bladder population of Lactobacilli that is markedly reduced. Exposing infected human BECs to L. crispatus in vitro markedly reduced the intracellular uropathogenic Escherichia coli (UPEC) load. The adherence of Lactobacilli to BECs was found to result in increased type I interferon (IFN) production, which in turn enhanced the expression of cathepsin D within lysosomes harboring UPECs. This lysosomal cathepsin D-mediated UPEC killing was diminished in germ-free mice and type I IFN receptor-deficient mice. Secreted metabolites of L. crispatus seemed to be responsible for the increased expression of type I IFN in human BECs. Intravesicular administration of Lactobacilli into UPEC-infected murine bladders markedly reduced their intracellular bacterial load suggesting that components of the endogenous microflora can have therapeutic effects against UTIs.
- Subjects :
- Animals
Biological Therapy
Cathepsin D metabolism
Female
Humans
Immunity, Innate
Male
Mice
Antibiosis
Escherichia coli Infections immunology
Escherichia coli Infections microbiology
Escherichia coli Infections therapy
Interferon Type I immunology
Lactobacillus crispatus physiology
Urinary Bladder immunology
Urinary Bladder microbiology
Urinary Tract Infections immunology
Urinary Tract Infections microbiology
Urinary Tract Infections therapy
Uropathogenic Escherichia coli growth & development
Subjects
Details
- Language :
- English
- ISSN :
- 1091-6490
- Volume :
- 119
- Issue :
- 33
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 35939684
- Full Text :
- https://doi.org/10.1073/pnas.2117904119