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

Peres, Newton G., Wang, Nancy, Whitney, Paul, Engel, Sven, Shreenivas, Meghanashree M., Comerford, Ian, Hocking, Dianna M., Erazo, Anna B., Forster, Irmgard, Kupz, Andreas, Gebhardt, Thomas, McColl, Shaun R., McSorley, Stephen J., Bedoui, Sammy, and Strugnell, Richard A. (2021) CD4+ T cell immunity to Salmonella is transient in the circulation. PLoS Pathogens. (In Press)

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Abstract

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.

Item ID: 69840
Item Type: Article (Research - C1)
ISSN: 1553-7374
Copyright Information: © 2021 Peres et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funders: Australian Research Council (ARC)
Projects and Grants: ARC DP200103110
Date Deposited: 01 Nov 2021 02:03
FoR Codes: 31 BIOLOGICAL SCIENCES > 3107 Microbiology > 310702 Infectious agents @ 40%
32 BIOMEDICAL AND CLINICAL SCIENCES > 3202 Clinical sciences > 320211 Infectious diseases @ 40%
32 BIOMEDICAL AND CLINICAL SCIENCES > 3204 Immunology > 320407 Innate immunity @ 20%
SEO Codes: 28 EXPANDING KNOWLEDGE > 2801 Expanding knowledge > 280102 Expanding knowledge in the biological sciences @ 65%
20 HEALTH > 2001 Clinical health > 200104 Prevention of human diseases and conditions @ 35%
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