Bifidobacteria shape antimicrobial T-helper cell responses during infancy and adulthood

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.

Human milk oligosaccharides regulate human macrophage polarization and activation in response to Staphylococcus aureus

“…Vogel et al. showed that S. aureus enhanced a Th1 response, whereas Bifidobacterium , a classic infant-associated bacteria, had a mitigating effect on this immune response ( 64 ). HMOs are known to have a bifidogenic effect and can therefore indirectly support this microbiome-driven immune regulation.…”

Human Breast Milk: The Role of Its Microbiota and Metabolites in Infant Health

“…Breastfeeding practices are identified as central factors in influencing the structure of breast milk microbiota, as the microbiota in infant’s oral cavity reciprocally influence the microbial composition of breast milk by retrograde inoculation. In this process, microbes from the infant’s oral cavity are transferred to the breast during breastfeeding, subsequently colonizing the mammary gland, contributing to reshaping the breast milk microbiota. , In summary, these studies have provided insights into the characteristics and major factors influencing microbial communities in breast milk, which can have a significant impact on the health and growth of the infant, including immune system maturation and digestive function. ,, However, it is important to recognize that the diversity and evolutionary aspects of the microbial community in breast milk are complex and require further exploration. Current research primarily focuses on microbial taxonomy and abundance studies, while there is a need for a deeper understanding of their biological functions and interactions.…”

“…Vogel and collaborators (2023) reported that the gut bifidobacteria population can shape antibacterial Th-cell responses during infancy. These bacteria can modulate T cells by inducing FoxP3+CD4+T cells, elevating IL-10 and galectin-1 secretion, and exerting CTLA-dependent suppression, thereby inhibiting Staphylococcus -specific Th cell activation through a cell-dependent mechanism . From breast milk to the infantile gut, bifidobacteria fortify infantile immune responses, providing an early immunological shield through intricate interactions with other microorganisms and host cells.…”

“…3,13 In summary, these studies have provided insights into the characteristics and major factors influencing microbial communities in breast milk, which can have a significant impact on the health and growth of the infant, including immune system maturation and digestive function. 3,17,57 However, it is important to recognize that the diversity and evolutionary aspects of the microbial community in breast milk are complex and require further exploration. Current research primarily focuses on microbial taxonomy and abundance studies, while there is a need for a deeper understanding of their biological functions and interactions.…”

“…Second, microbial metabolites, such as SCFAs, help regulate intestinal T-cell responses, promoting immune tolerance . Moreover, microbes in breast milk, especially probiotics, can stimulate immune cells in the neonatal intestines, such as mucosa-associated lymphocytes, enhancing the host’s immune response ,, (Figure ). Additionally, breastfeeding supports the long-term development of the infant’s immune system by regulating beneficial SCFA-producing bacteria in neonatal gut …”