Abstract
AbstractMicrobial infections early in life are challenging for the unexperienced immune system. The SARS-CoV-2 pandemic again has highlighted that neonatal, infant, child, and adult T-helper(Th)-cells respond differently to infections, and requires further understanding. This study investigates anti-bacterial T-cell responses against Staphylococcus aureus aureus, Staphylococcus epidermidis and Bifidobacterium longum infantis in early stages of life and adults and shows age and pathogen-dependent mechanisms. Beside activation-induced clustering, T-cells stimulated with Staphylococci become Th1-type cells; however, this differentiation is mitigated in Bifidobacterium-stimulated T-cells. Strikingly, prestimulation of T-cells with Bifidobacterium suppresses the activation of Staphylococcus-specific T-helper cells in a cell-cell dependent manner by inducing FoxP3+CD4+ T-cells, increasing IL-10 and galectin-1 secretion and showing a CTLA-4-dependent inhibitory capacity. Furthermore Bifidobacterium dampens Th responses of severely ill COVID-19 patients likely contributing to resolution of harmful overreactions of the immune system. Targeted, age-specific interventions may enhance infection defence, and specific immune features may have potential cross-age utilization.
Funder
Deutsche Forschungsgemeinschaft
Bundesministerium für Bildung und Forschung
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
Reference67 articles.
1. World Health Organization. Children: reducing mortality. Fact sheets. Available at http://www.who.int/en/news-room/fact-sheets/detail/children-reducing-mortality (2017).
2. Sharma, A. A., Jen, R., Butler, A. & Lavoie, P. M. The developing human preterm neonatal immune system: a case for more research in this area. Proc. Natl Acad. Sci. USA 145, 61–68 (2012).
3. Arra, A. et al. Immune-checkpoint blockage of CTLA-4 (CD152) in antigen-specific human T-cell responses differs profoundly between neonates, children, and adults. OncoImmunology 10, 1938475 (2021).
4. Hebel, K. et al. CD4+ T cells from human neonates and infants are poised spontaneously to run a nonclassical IL-4 program. J. Immunol. 192, 5160–5170 (2014).
5. Knolle, J. et al. Children from the age of three show a developmental switch in T-cell differentiation. Front. Immunol. 11, 1640 (2020).
Cited by
6 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