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

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.
Competing Interests: AP-N and TS have a patent of the RISK6 signature pending. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor declared a past co-authorship with several of the authors, TS and MH.
(Copyright © 2021 Baguma, Mbandi, Rodo, Erasmus, Day, Makhethe, de Kock, van Rooyen, Stone, Bilek, Steyn, Africa, Darboe, Chegou, Tromp, Walzl, Hatherill, Penn-Nicholson and Scriba.)