Bifidobacteria shape antimicrobial T-helper cell responses during infancy and adulthood
Katrin Vogel, Aditya Arra, Holger Lingel, Dirk Bretschneider, Florian Prätsch, Denny Schanze, Martin Zenker, Silke Balk, Dunja Bruder, Robert Geffers, Thomas Hachenberg, Christoph Arens, Monika C. Brunner‐Weinzierl
Abstract
Abstract Microbial 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.