Rapaka, R.R, Wahid, R., Fresnay, S. et al. (7 more authors) (2020) Human Salmonella Typhi exposure generates differential multifunctional cross‐reactive T‐cell memory responses against Salmonella Paratyphi and invasive nontyphoidal Salmonella. Clinical & Translational Immunology, 9 (9). e1178. ISSN 2050-0068
Abstract
Objective
There are no vaccines for most of the major invasive Salmonella strains causing severe infection in humans. We evaluated the specificity of adaptive T memory cell responses generated after Salmonella Typhi exposure in humans against other major invasive Salmonella strains sharing capacity for dissemination.
Methods
T memory cells from eleven volunteers who underwent controlled oral challenge with wt S. Typhi were characterised by flow cytometry for cross‐reactive cellular cytokine/chemokine effector responses or evidence of degranulation upon stimulation with autologous B‐lymphoblastoid cells infected with either S. Typhi, Salmonella Paratyphi A (PA), S. Paratyphi B (PB) or an invasive nontyphoidal Salmonella strain of the S. Typhimurium serovar (iNTSTy).
Results
Blood T‐cell effector memory (TEM) responses after exposure to S. Typhi in humans evolve late, peaking weeks after infection in most volunteers. Induced multifunctional CD4+ Th1 and CD8+ TEM cells elicited after S. Typhi challenge were cross‐reactive with PA, PB and iNTSTy. The magnitude of multifunctional CD4+ TEM cell responses to S. Typhi correlated with induction of cross‐reactive multifunctional CD8+ TEM cells against PA, PB and iNTSTy. Highly multifunctional subsets and T central memory and T effector memory cells that re‐express CD45 (TEMRA) demonstrated less heterologous T‐cell cross‐reactivity, and multifunctional Th17 elicited after S. Typhi challenge was not cross‐reactive against other invasive Salmonella.
Conclusion
Gaps in cross‐reactive immune effector functions in human T‐cell memory compartments were highly dependent on invasive Salmonella strain, underscoring the importance of strain‐dependent vaccination in the design of T‐cell‐based vaccines for invasive Salmonella.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2020 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc. This is an open access article under the terms of the Creative Commons Attribution License, (http://creativecommons.org/licenses/by/4.0) which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
Keywords: | human challenge; iNTS; invasive Salmonella; Paratyphi; S. Typhi; T‐cell memory |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Sheffield Teaching Hospitals |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 19 Oct 2020 13:39 |
Last Modified: | 19 Oct 2020 13:39 |
Status: | Published |
Publisher: | Wiley |
Refereed: | Yes |
Identification Number: | 10.1002/cti2.1178 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:166461 |