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Tissue-resident memory T cells mediate mucosal immunity to recurrent urinary tract infection. | LitMetric

Tissue-resident memory T cells mediate mucosal immunity to recurrent urinary tract infection.

Sci Immunol

Mucosal Inflammation and Immunity, Department of Immunology, Institut Pasteur, Inserm U1223, Paris 75015, France.

Published: May 2023

AI Article Synopsis

  • Urinary tract infections (UTIs) are common, and there's an urgent need for new treatments due to rising antibiotic resistance.
  • Research showed that reducing the bacterial load early in infection eliminated the protective immune memory response, but T cell polarization remained unchanged.
  • A specific group of memory T cells in the bladder mucosa was found to be critical for immune protection, pointing to the potential for T-cell-targeted therapies or vaccines to prevent recurrent UTIs without antibiotics.

Article Abstract

Urinary tract infection (UTI) is one of the most prevalent human bacterial infections. New therapeutic approaches, including vaccination and immunotherapy, are urgently needed to combat the rapid global dissemination of multidrug-resistant uropathogens. Development of therapies is impeded by an incomplete understanding of memory development during UTI. Here, we found that reducing bacterial load early in infection, by reducing the inoculum or with antibiotics after infection, completely abrogated the protective memory response. We observed a mixed T helper (T) cell polarization, composed of T1, T2, and T17 T cells, among T cells infiltrating the bladder during primary infection. Thus, we hypothesized that reducing antigen load altered T cell polarization, leading to poor memory. Unexpectedly, however, T cell polarization was unchanged in these scenarios. Instead, we uncovered a population of tissue-resident memory (T) T cells that was significantly reduced in the absence of sufficient antigen. Demonstrating that T cells are necessary for immune memory, transfer of lymph node- or spleen-derived infection-experienced T cells to naïve animals did not confer protection against infection. Supporting that T cells are sufficient to protect against recurrent UTI, animals depleted of systemic T cells, or treated with FTY720 to block memory lymphocyte migration from lymph nodes to infected tissue, were equally protected compared with unmanipulated mice against a second UTI. Thus, we uncovered an unappreciated key role for T cells in the memory response to bacterial infection in the bladder mucosa, providing a target for non-antibiotic-based immunotherapy and/or new vaccine strategies to prevent recurrent UTI.

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Source
http://dx.doi.org/10.1126/sciimmunol.abn4332DOI Listing

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