Available online 20 June 2022, 104572

First demonstration of cytokine-secreting MAIT cell kinetics after human challenge with Salmonella enterica serovar Typhi.

MAIT cell's functional signatures and association with typhoid fever protection.

Predictive value of MAIT cell cytokine pattern.

Lack of association between the number of cytokines expressed by MAIT cells and prevention against typhoid fever.

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.

MAIT cells

human

polyfunctionality

disease status

bacteria

Salmonella

Mucosal-Associated Invariant T cells

Salmonella enterica serovar Typhi

participants who had fever ≥38°C followed by S. Typhi isolation from blood

participants who did not meet the typhoid fever definition

© 2022 The Author(s). Published by Elsevier Inc.