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

      Rapaka, Rekha R; Wahid, Rezwanul; Fresnay, Stephanie; Booth, Jayaum S; Darton, Thomas C; Jones, Claire; Waddington, Claire S; Levine, Myron M; Pollard, Andrew J; Sztein, Marcelo B (Wiley-Blackwell, 2020-09-24)
      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.
    • Mucosal-Associated Invariant T cells exhibit distinct functional signatures associated with protection against typhoid fever.

      Salerno-Gonçalves, Rosângela; Fresnay, Stephanie; Magder, Laurence; Darton, Thomas C; Waddington, Claire S; Blohmke, Christoph J; Angus, Brian; Levine, Myron M; Pollard, Andrew J; Sztein, Marcelo B (Elsevier, 2022-06-20)
      We have previously demonstrated that Mucosal-Associated Invariant T (MAIT) cells secrete multiple cytokines after exposure to Salmonella enterica serovar Typhi (S. Typhi), the causative agent of typhoid fever in humans. However, whether cytokine secreting MAIT cells can enhance or attenuate the clinical severity of bacterial infections remain debatable. This study characterizes human MAIT cell functions in subjects participating in a wild-type S. Typhi human challenge model. Here, we found that MAIT cells exhibit distinct functional signatures associated with protection against typhoid fever. We also observed that the cytokine patterns of MAIT cell responses, rather than the average number of cytokines expressed, are more predictive of typhoid fever outcomes. These results might enable us to objectively, based on functional parameters, identify cytokine patterns that may serve as predictive biomarkers during natural infection and vaccination.