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

3 Citations (Scopus)

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

Fingerprint

Th1 Cells
Salmonella Infections
Adoptive Transfer
Immunity
Salmonella Vaccines
T-Lymphocytes
Lymphocyte Function-Associated Antigen-1
Liver
Salmonella
Epitopes
Vaccines
Bacteria
Infection

Keywords

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

ASJC Scopus subject areas

  • General

Cite this

Optimal protection against Salmonella infection requires noncirculating memory. / Benoun, Joseph M.; Peres, Newton G.; Wang, Nancy; Pham, Oanh H.; Rudisill, Victoria L.; Fogassy, Zachary N.; Whitney, Paul G.; Fernandez-Ruiz, Daniel; Gebhardt, Thomas; Pham, Quynh Mai; Puddington, Lynn; Bedoui, Sammy; Strugnell, Richard A.; Mcsorley, Stephen J.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 115, No. 41, 09.10.2018, p. 10416-10421.

Research output: Contribution to journalArticle

Benoun, JM, Peres, NG, Wang, N, Pham, OH, Rudisill, VL, Fogassy, ZN, Whitney, PG, Fernandez-Ruiz, D, Gebhardt, T, Pham, QM, Puddington, L, Bedoui, S, Strugnell, RA & Mcsorley, SJ 2018, 'Optimal protection against Salmonella infection requires noncirculating memory', Proceedings of the National Academy of Sciences of the United States of America, vol. 115, no. 41, pp. 10416-10421. https://doi.org/10.1073/pnas.1808339115
Benoun, Joseph M. ; Peres, Newton G. ; Wang, Nancy ; Pham, Oanh H. ; Rudisill, Victoria L. ; Fogassy, Zachary N. ; Whitney, Paul G. ; Fernandez-Ruiz, Daniel ; Gebhardt, Thomas ; Pham, Quynh Mai ; Puddington, Lynn ; Bedoui, Sammy ; Strugnell, Richard A. ; Mcsorley, Stephen J. / Optimal protection against Salmonella infection requires noncirculating memory. In: Proceedings of the National Academy of Sciences of the United States of America. 2018 ; Vol. 115, No. 41. pp. 10416-10421.
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