A highly polarized TH2 bladder response to infection promotes epithelial repair at the expense of preventing new infections

Jianxuan Wu, Byron W. Hayes, Cassandra Phoenix, Gustavo Sosa Macias, Yuxuan Miao, Hae Woong Choi, Francis M. Hughes, J. Todd Purves, R. Lee Reinhardt, Soman N. Abraham

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Urinary tract infections (UTIs) typically evoke prompt and vigorous innate bladder immune responses, including extensive exfoliation of the epithelium. To explain the basis for the extraordinarily high recurrence rates of UTIs, we examined adaptive immune responses in mouse bladders. We found that, following each bladder infection, a highly T helper type 2 (TH2)–skewed immune response directed at bladder re-epithelialization is observed, with limited capacity to clear infection. This response is initiated by a distinct subset of CD301b+OX40L+ dendritic cells, which migrate into the bladder epithelium after infection before trafficking to lymph nodes to preferentially activate TH2 cells. The bladder epithelial repair response is cumulative and aberrant as, after multiple infections, the epithelium was markedly thickened and bladder capacity was reduced relative to controls. Thus, recurrence of UTIs and associated bladder dysfunction are the outcome of the preferential focus of the adaptive immune response on epithelial repair at the expense of bacterial clearance.

Original languageEnglish
Pages (from-to)671-683
Number of pages13
JournalNature Immunology
Volume21
Issue number6
DOIs
Publication statusPublished - 2020 Jun 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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