4.8 Article

Circulating immunity protects the female reproductive tract from Chlamydia infection

Publisher

NATL ACAD SCIENCES
DOI: 10.1073/pnas.2104407118

Keywords

female reproductive tract; CD4 T cells; Chlamydia

Funding

  1. National Institute of Allergy and Infectious Diseases [R01AI103433, R01AI139047, R01AI139410, T32AI060555]
  2. Sims Immunology Fellowship

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Barrier tissues can be protected from infections such as Chlamydia via circulating immune memory, even in the absence of tissue-resident immune cells. Blocking the rapid mobilization of circulating memory CD4 T cells to the female reproductive tract inhibits this protective response. This provides an unexpected opportunity for vaccine development against infections of the female reproductive tract.
Anatomical positioning of memory lymphocytes within barrier tissues accelerates secondary immune responses and is thought to be essential for protection at mucosal surfaces. However, it remains unclear whether resident memory in the female reproductive tract (FRT) is required for Chlamydial immunity. Here, we describe efficient generation of tissue-resident memory CD4 T cells and memory lymphocyte clusters within the FRT after vaginal infection with Chlamydia. Despite robust establishment of localized memory lymphocytes within the FRT, naive mice surgically joined to immune mice, or mice with only circulating immunity following intranasal immunization, were fully capable of resisting Chlamydia infection via the vaginal route. Blocking the rapid mobilization of circulating memory CD4 T cells to the FRT inhibited this protective response. These data demonstrate that secondary protection in the FRT can occur in the complete absence of tissue-resident immune cells. The ability to confer robust protection to barrier tissues via circulating immune memory provides an unexpected opportunity for vaccine development against infections of the FRT.

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