Optimal protection against Salmonella infection requires noncirculating memory

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 115; no. 41; pp. 10416 - 10421
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 09.10.2018
• Subjects: Adoptive transfer; Animal tissues; Animals; Bacteria; Biological Sciences; Blood circulation; CD4 antigen; Cells; Cells, Cultured; Computer memory; Epitopes; Female; Hepatocytes; Immunity; Immunization; Immunologic Memory - immunology; Immunological memory; Infections; LFA-1 antigen; Liver; Liver - immunology; Liver - microbiology; Lymphocytes; Lymphocytes T; Memory; Memory cells; Mice; Mice, Inbred C57BL; Salmonella; Salmonella Infections - immunology; Salmonella Infections - microbiology; Salmonella Infections - prevention & control; Salmonella typhimurium - immunology; Studies; T-Lymphocytes - immunology; T-Lymphocytes - microbiology; Th1 Cells - immunology; Th1 Cells - microbiology; Vaccines; γ-Interferon; Salmonella infection; CD4 T cell; vaccines; tissue-resident memory; protective immunity
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1808339115

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.