Author:
Baguma Richard,Mbandi Stanley Kimbung,Rodo Miguel J.,Erasmus Mzwandile,Day Jonathan,Makhethe Lebohang,de Kock Marwou,van Rooyen Michele,Stone Lynnett,Bilek Nicole,Steyn Marcia,Africa Hadn,Darboe Fatoumatta,Chegou Novel N.,Tromp Gerard,Walzl Gerhard,Hatherill Mark,Penn-Nicholson Adam,Scriba Thomas J.
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.
Funder
European and Developing Countries Clinical Trials Partnership
Horizon 2020
Subject
Immunology,Immunology and Allergy
Reference61 articles.
1. The Wonder Years: What Can Primary School Children Teach Us About Immunity to Mycobacterium tuberculosis;Seddon;Front Immunol,2018
2. Childhood Pulmonary Tuberculosis;Marais;Am J Respir Crit Care Med,2006
3. The natural history of childhood intra-thoracic tuberculosis: A critical review of literature from the pre-chemotherapy era;Marais;Int J Tuberc Lung Dis,2004
4. Tuberculosis in children;Perez-Velez;New Engl J Med,2012
Cited by
7 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献