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

Publication ,  Journal Article
Wu, J; Hayes, BW; Phoenix, C; Macias, GS; Miao, Y; Choi, HW; Hughes, FM; Todd Purves, J; Lee Reinhardt, R; Abraham, SN
Published in: Nat Immunol
June 2020

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.

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Published In

Nat Immunol

DOI

EISSN

1529-2916

Publication Date

June 2020

Volume

21

Issue

6

Start / End Page

671 / 683

Location

United States

Related Subject Headings

  • Wound Healing
  • Urinary Tract Infections
  • Th2 Cells
  • Th1 Cells
  • Mucous Membrane
  • Mice, Knockout
  • Mice
  • Lymphocyte Activation
  • Immunology
  • Female
 

Citation

APA
Chicago
ICMJE
MLA
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Wu, J., Hayes, B. W., Phoenix, C., Macias, G. S., Miao, Y., Choi, H. W., … Abraham, S. N. (2020). A highly polarized TH2 bladder response to infection promotes epithelial repair at the expense of preventing new infections. Nat Immunol, 21(6), 671–683. https://doi.org/10.1038/s41590-020-0688-3
Wu, Jianxuan, Byron W. Hayes, Cassandra Phoenix, Gustavo Sosa Macias, Yuxuan Miao, Hae Woong Choi, Francis M. Hughes, J. Todd Purves, R. Lee Reinhardt, and Soman N. Abraham. “A highly polarized TH2 bladder response to infection promotes epithelial repair at the expense of preventing new infections.Nat Immunol 21, no. 6 (June 2020): 671–83. https://doi.org/10.1038/s41590-020-0688-3.
Wu J, Hayes BW, Phoenix C, Macias GS, Miao Y, Choi HW, et al. A highly polarized TH2 bladder response to infection promotes epithelial repair at the expense of preventing new infections. Nat Immunol. 2020 Jun;21(6):671–83.
Wu, Jianxuan, et al. “A highly polarized TH2 bladder response to infection promotes epithelial repair at the expense of preventing new infections.Nat Immunol, vol. 21, no. 6, June 2020, pp. 671–83. Pubmed, doi:10.1038/s41590-020-0688-3.
Wu J, Hayes BW, Phoenix C, Macias GS, Miao Y, Choi HW, Hughes FM, Todd Purves J, Lee Reinhardt R, Abraham SN. 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.

Published In

Nat Immunol

DOI

EISSN

1529-2916

Publication Date

June 2020

Volume

21

Issue

6

Start / End Page

671 / 683

Location

United States

Related Subject Headings

  • Wound Healing
  • Urinary Tract Infections
  • Th2 Cells
  • Th1 Cells
  • Mucous Membrane
  • Mice, Knockout
  • Mice
  • Lymphocyte Activation
  • Immunology
  • Female