Optimal protection against Salmonella infection requires noncirculating memory

Joseph M. Benoun, Newton G. Peres, Nancy Wang, Oanh H. Pham, Victoria L. Rudisill, Zachary N. Fogassy, Paul G. Whitney, Daniel Fernandez-Ruiz, Thomas Gebhardt, Quynh Mai Pham, Lynn Puddington, Sammy Bedoui, Richard A. Strugnell, Stephen J Mcsorley

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)10416-10421
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume115
Issue number41
DOIs
StatePublished - Oct 9 2018

Keywords

  • CD4 T cell
  • Protective immunity
  • Salmonella infection
  • Tissue-resident memory
  • Vaccines

ASJC Scopus subject areas

  • General

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