Format

Send to

Choose Destination
Proc Natl Acad Sci U S A. 2018 Oct 9;115(41):10416-10421. doi: 10.1073/pnas.1808339115. Epub 2018 Sep 25.

Optimal protection against Salmonella infection requires noncirculating memory.

Author information

1
Center for Comparative Medicine, University of California, Davis, CA 95616.
2
Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California, Davis, CA 95616.
3
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC 3000, Australia.
4
Department of Immunology, University of Connecticut Health Center, Farmington, CT 06030.
5
Center for Comparative Medicine, University of California, Davis, CA 95616; sjmcsorley@ucdavis.edu.

Abstract

While CD4 Th1 cells are required for resistance to intramacrophage infections, adoptive transfer of Th1 cells is insufficient to protect against Salmonella infection. Using an epitope-tagged vaccine strain of Salmonella, we found that effective protection correlated with expanded Salmonella-specific memory CD4 T cells in circulation and nonlymphoid tissues. However, naive mice that previously shared a blood supply with vaccinated partners lacked T cell memory with characteristics of tissue residence and did not acquire robust protective immunity. Using a YFP-IFN-γ reporter system, we identified Th1 cells in the liver of immunized mice that displayed markers of tissue residence, including P2X7, ARTC2, LFA-1, and CD101. Adoptive transfer of liver memory cells after ARTC2 blockade increased protection against highly virulent bacteria. Taken together, these data demonstrate that noncirculating memory Th1 cells are a vital component of immunity to Salmonella infection and should be the focus of vaccine strategies.

KEYWORDS:

CD4 T cell; Salmonella infection; protective immunity; tissue-resident memory; vaccines

PMID:
30254173
PMCID:
PMC6187142
[Available on 2019-04-09]
DOI:
10.1073/pnas.1808339115
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center