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

Content Provider	Directory of Open Access Journals (DOAJ)
Author	Miguel J. Rodo Mzwandile Erasmus Richard Baguma Stanley Kimbung Mbandi Jonathan Day Lebohang Makhethe Marwou de Kock Michele van Rooyen Lynnett Stone Nicole Bilek Marcia Steyn Hadn Africa Fatoumatta Darboe Novel N. Chegou Gerard Tromp Gerhard Walzl Mark Hatherill Adam Penn-Nicholson Thomas J. Scriba
Abstract	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.
e-ISSN	16643224
DOI	10.3389/fimmu.2021.639965
Journal	Frontiers in Immunology
Volume Number	12
Language	English
Publisher	Frontiers Media S.A.
Publisher Date	2021-02-01
Publisher Place	Switzerland
Access Restriction	Open
Subject Keyword	Immunologic Diseases. Allergy Inflammation Tuberculosis Anti-mycobacterial Immunity Age Pediatric
Content Type	Text
Resource Type	Article

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