Metabolites enhance innate resistance to human Mycobacterium tuberculosis infection.

ABSTRACT: To determine the mechanisms that mediate resistance to Mycobacterium tuberculosis (M. tuberculosis) infection in household contacts (HHCs) of patients with tuberculosis (TB), we followed 452 latent TB infection-negative (LTBI-) HHCs for 2 years. Those who remained LTBI- throughout the study were identified as nonconverters. At baseline, nonconverters had a higher percentage of CD14+ and CD3-CD56+CD27+CCR7+ memory-like natural killer (NK) cells. Using a whole-transcriptome and metabolomic approach, we identified deoxycorticosterone acetate as a metabolite with elevated concentrations in the plasma of nonconverters, and further studies showed that this metabolite enhanced glycolytic ATP flux in macrophages and restricted M. tuberculosis growth by enhancing antimicrobial peptide production th

SUBMITTER: Tripathi D 

PROVIDER: S-EPMC9746823 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature