Open AccessCD4+ T cell immunity to Salmonella is transient in the circulation
Author(s) -
Newton G. Peres,
Nancy Wang,
Paul G. Whitney,
Sven Engel,
Meghanashree M. Shreenivas,
Ian Comerford,
Dianna M Hocking,
Anna Belen Erazo,
Irmgard Förster,
Andreas Kupz,
Thomas Gebhardt,
Shaun R. McColl,
Stephen J. McSorley,
Sammy Bedoui,
Richard A. Strugnell
Publication year - 2021
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1010004
Subject(s) - salmonella enterica , salmonella , biology , adoptive cell transfer , immunity , microbiology and biotechnology , intracellular parasite , t cell , acquired immune system , immunology , chemokine , immune system , bacteria , genetics
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.