<p>CD4<sup>+</sup> T cells are necessary to control intracellular bacterial infections, but the role of sex in these infections is poorly understood. Here we show that upon challenge with <i>Salmonella</i>, a model intracellular bacterium, more male mice succumb to infection than females, despite having more <i>Salmonella</i> specific CD4<sup>+</sup> T cells at later infection stages. Upon infecting mice lacking CD4<sup>+</sup> T cells, survival differences reverse, which suggests that female and male CD4<sup>+</sup> T cells play opposing roles during infection. Transfer of purified CD4<sup>+</sup> T cells from either sex into CD4 deficient mice restores survival in females but decreases survival in males. Decreasing the hormone 17β-estradiol in females induces a more severe male-like phenotype. Exogenous 17β-estradiol induces both inflammatory and suppressive cytokines in CD4<sup>+</sup> T cells from infected female mice and restores the protective function of T cells during infection. These findings reveal a sex difference in CD4<sup>+</sup> T cell behavior during intracellular bacterial infection.</p>

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CD4+ T cell protection against murine Salmonella infection is female-specific and estrogen-dependent

  • Shaina J. D’Souza,
  • Rebecca M. Horowitz,
  • Louay Bachnak,
  • Victoria E. Immethun,
  • Matthew S. Godwin,
  • Charlotte M. Hankin,
  • Vanessa M. Limbert,
  • David L. Bauer,
  • Alex J. Plaisance,
  • Avery M. Burke,
  • Lisa A. Morici,
  • Hyemin Lee,
  • Hua Lu,
  • Ryan Craig,
  • Jonathan R. Kurtz,
  • Sophia A. Blessinger,
  • Sarah H. Lindsey,
  • Franck Mauvais-Jarvis,
  • Ali Yasrebi,
  • Victoria Appel,
  • Troy A. Roepke,
  • John A. McLachlan,
  • James B. McLachlan

摘要

CD4+ T cells are necessary to control intracellular bacterial infections, but the role of sex in these infections is poorly understood. Here we show that upon challenge with Salmonella, a model intracellular bacterium, more male mice succumb to infection than females, despite having more Salmonella specific CD4+ T cells at later infection stages. Upon infecting mice lacking CD4+ T cells, survival differences reverse, which suggests that female and male CD4+ T cells play opposing roles during infection. Transfer of purified CD4+ T cells from either sex into CD4 deficient mice restores survival in females but decreases survival in males. Decreasing the hormone 17β-estradiol in females induces a more severe male-like phenotype. Exogenous 17β-estradiol induces both inflammatory and suppressive cytokines in CD4+ T cells from infected female mice and restores the protective function of T cells during infection. These findings reveal a sex difference in CD4+ T cell behavior during intracellular bacterial infection.