Lactobacillus crispatus Limits Bladder Uropathogenic E. coli Infection by Triggering a Host Type I Interferon Response

Chang Hyun Song, Young Ho Kim, Manisha Naskar, Byron W. Hayes, Mathew A. Abraham, Joo Hwan Noh, Gyeongseo Suk, Min Jung Kim, Kyu Sang Cho, Minhye Shin, Eun Jin Lee, Soman N. Abraham, Hae Woong Choi

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

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.

Original languageEnglish
Article numbere2117904119
JournalProceedings of the National Academy of Sciences of the United States of America
Volume119
Issue number33
DOIs
Publication statusPublished - 2022 Aug 16

Keywords

  • Lactobacilli
  • commensal bacteria
  • interferon
  • type
  • urinary tract infection

ASJC Scopus subject areas

  • General

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