BMDM from Young and Aged Mice Treated with β-glucan

Advancing age significantly heightens the incidence and severity of infection, with individuals aged 65 and above, accounting for 65% of sepsis cases. The decline in immune response with age, termed “immunosenescence”, heightens vulnerability to infection and sepsis. This prompts exploration of strategies to enhance infection resistance by modulating the aging immune system. Innate immune training, referred to as “trained immunity” or “innate immune memory”, emerges as a potential strategy. We investigated the impact of 𝛽-glucan induced innate immune training on aged mice (18–20 months old), compared with a group of young mice (10–12 weeks old). We found that 𝛽-glucan augmented host’s resistance to infection. This enhancement was characterized by preservation of body temperature during infection, improved leukocyte recruitment, augmented bacterial clearance, and decreased cytokine production both in blood and infection sites. Furthermore, trained macrophages displayed heightened metabolic capacity and improved antimicrobial functions such as enhanced phagocytosis and respiratory burst. RNA-seq analysis underscored a distinctive gene expression pattern induced by trained immunity in macrophages, consistently observed in both young and aged groups. Our results suggest that immune training can be effectively induced in aging individuals, providing valuable insights into potential strategies for enhancing infection resistance in the elderly. Bone marrow-derived macrophages from WT C57BL/6 mice were treated with β-glucan, lipopolysaccaride (LPS), vehicle (normal saline (NS)), or multiple treatments in sequence. We then performed gene expression profile analysis from 3 biological replicates per treatment at multiple timepoints. The effects on the transciptome were compared between groups.