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 journalArticle

8 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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  • Cite this

    Benoun, J. M., Peres, N. G., Wang, N., Pham, O. H., Rudisill, V. L., Fogassy, Z. N., Whitney, P. G., Fernandez-Ruiz, D., Gebhardt, T., Pham, Q. M., Puddington, L., Bedoui, S., Strugnell, R. A., & Mcsorley, S. J. (2018). Optimal protection against Salmonella infection requires noncirculating memory. Proceedings of the National Academy of Sciences of the United States of America, 115(41), 10416-10421. https://doi.org/10.1073/pnas.1808339115