PLoS Pathogens (Oct 2021)

CD4+ T cell immunity to Salmonella is transient in the circulation.

  • Newton G Peres,
  • Nancy Wang,
  • Paul Whitney,
  • Sven Engel,
  • Meghanashree M Shreenivas,
  • Ian Comerford,
  • Dianna M Hocking,
  • Anna B Erazo,
  • Irmgard Förster,
  • Andreas Kupz,
  • Thomas Gebhardt,
  • Shaun R McColl,
  • Stephen J McSorley,
  • Sammy Bedoui,
  • Richard A Strugnell

DOI
https://doi.org/10.1371/journal.ppat.1010004
Journal volume & issue
Vol. 17, no. 10
p. e1010004

Abstract

Read online

While Salmonella enterica is seen as an archetypal facultative intracellular bacterial pathogen where protection is mediated by CD4+ T cells, identifying circulating protective cells has proved very difficult, inhibiting steps to identify key antigen specificities. Exploiting a mouse model of vaccination, we show that the spleens of C57BL/6 mice vaccinated with live-attenuated Salmonella serovar Typhimurium (S. Typhimurium) strains carried a pool of IFN-γ+ CD4+ T cells that could adoptively transfer protection, but only transiently. Circulating Salmonella-reactive CD4+ T cells expressed the liver-homing chemokine receptor CXCR6, accumulated over time in the liver and assumed phenotypic characteristics associated with tissue-associated T cells. Liver memory CD4+ T cells showed TCR selection bias and their accumulation in the liver could be inhibited by blocking CXCL16. These data showed that the circulation of CD4+ T cells mediating immunity to Salmonella is limited to a brief window after which Salmonella-specific CD4+ T cells migrate to peripheral tissues. Our observations highlight the importance of triggering tissue-specific immunity against systemic infections.