1 research outputs found
Human Salmonella Typhi exposure generates differential multifunctional crossâreactive Tâcell memory responses against Salmonella Paratyphi and invasive nontyphoidal Salmonella
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 crossâreactive cellular cytokine/chemokine effector responses or evidence of degranulation upon stimulation with autologous Bâlymphoblastoid 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 Tâcell 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 crossâreactive with PA, PB and iNTSTy. The magnitude of multifunctional CD4+ TEM cell responses to S. Typhi correlated with induction of crossâreactive multifunctional CD8+ TEM cells against PA, PB and iNTSTy. Highly multifunctional subsets and T central memory and T effector memory cells that reâexpress CD45 (TEMRA) demonstrated less heterologous Tâcell crossâreactivity, and multifunctional Th17 elicited after S. Typhi challenge was not crossâreactive against other invasive Salmonella.
Conclusion
Gaps in crossâreactive immune effector functions in human Tâcell memory compartments were highly dependent on invasive Salmonella strain, underscoring the importance of strainâdependent vaccination in the design of Tâcellâbased vaccines for invasive Salmonella