Human Salmonella Typhi exposure generates differential multifunctional cross-reactive T-cell memory responses against Salmonella Paratyphi and invasive nontyphoidal Salmonella

Objective: <br>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 sharin...

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主要な著者: Rapaka, RR, Wahid, R, Fresnay, S, Booth, JS, Darton, TC, Jones, C, Waddington, CS, Levine, MM, Pollard, AJ, Sztein, MB
フォーマット: Journal article
言語:English
出版事項: Wiley Open Access 2020
その他の書誌記述
要約:Objective: <br>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. <br><br>Methods: <br>T memory cells from eleven volunteers who underwent controlled oral challenge with wtS.&#xA0;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.&#xA0;Typhi, Salmonella Paratyphi A (PA), S.&#xA0;Paratyphi B (PB) or an invasive nontyphoidal Salmonella strain of the S.&#xA0;Typhimurium serovar (iNTSTy). <br><br>Results: <br>Blood T-cell effector memory (TEM) responses after exposure to S.&#xA0;Typhi in humans evolve late, peaking weeks after infection in most volunteers. Induced multifunctional CD4+ Th1 and CD8+ TEM cells elicited after S.&#xA0;Typhi challenge were cross-reactive with PA, PB and iNTSTy. The magnitude of multifunctional CD4+ TEM cell responses to S.&#xA0;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.&#xA0;Typhi challenge was not cross-reactive against other invasive Salmonella. <br><br>Conclusion:<br> 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.