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

Nat Immunol. 2020 Jun;21(6):671-683. doi: 10.1038/s41590-020-0688-3. Epub 2020 May 18.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bacterial Load
  • Biomarkers
  • Cell Line
  • Cystitis / etiology*
  • Cystitis / metabolism*
  • Cystitis / pathology
  • Cytokines / metabolism
  • Disease Models, Animal
  • Female
  • Lymphocyte Activation / immunology*
  • Mice
  • Mice, Knockout
  • Mucous Membrane / immunology*
  • Mucous Membrane / metabolism*
  • Mucous Membrane / pathology
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Th1 Cells / pathology
  • Th2 Cells / immunology*
  • Th2 Cells / metabolism*
  • Urinary Tract Infections / etiology
  • Urinary Tract Infections / metabolism
  • Urinary Tract Infections / microbiology
  • Wound Healing / genetics
  • Wound Healing / immunology


  • Biomarkers
  • Cytokines