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The risk of progression from  Mycobacterium tuberculosis  ( M.tb)  infection to active tuberculosis (TB) disease varies markedly with age. TB disease is significantly less likely in pre-adolescent children above 4 years of age than in very young children or post-pubescent adolescents and young adults. We hypothesized that pro-inflammatory responses to  M.tb  in pre-adolescent children are either less pronounced or more regulated, than in young adults. Inflammatory and antimicrobial mediators, measured by microfluidic RT-qPCR and protein bead arrays, or by analyzing published microarray data from TB patients and controls, were compared in pre-adolescent children and adults. Multivariate analysis revealed that  M.tb -uninfected 8-year-old children had lower levels of myeloid-associated pro-inflammatory mediators than uninfected 18-year-old young adults. Relative to uninfected children, those with  M.tb -infection had higher levels of similar myeloid inflammatory responses. These inflammatory mediators were also expressed after  in vitro  stimulation of whole blood from uninfected children with live  M.tb . Our findings suggest that myeloid inflammation is intrinsically lower in pre-pubescent children than in young adults. The lower or more regulated pro-inflammatory responses may play a role in the lower risk of TB disease in this age group.

Inflammatory Determinants of Differential Tuberculosis Risk in Pre-Adolescent Children and Young Adults