beta-glucan induced training and tolerance: alterations to primary monocytes

In mice and humans, exposure to β-glucan can induce epigenetic reprograming in monocytes resulting in enhanced responses to heterologous agonists. Epigenetic reprograming is the basis for innate memory, which includes both decreased immune responsiveness (innate tolerance) and increased responsiveness (innate training). As a valuable food animal and medically relevant species, we sought to understand the phenotypic and mechanistic alterations induced by β-glucan on swine cells to develop methods to enhance health while limiting antibiotic usage. Thus, primary porcine monocytes were stimulated with β-glucan from S. cerevisiae or C. albicans , rested for 5 d, and then restimulated with lipopolysaccharide (LPS; TLR 4 agonist) or Pam 3 CSK 4 (synthetic triacylated lipopeptide; TLR 2 agonist) to determine trained or tolerant phenotype (increase or decrease in cytokine production relative to unstimulated controls). Zymosan (β-glucan from S. cerevisiae ) primed monocytes exhibited a tolerant phenotype (decreased IL-1β and TNF-α production compared to controls) when restimulated with LPS or Pam 3 CSK 4 . However, β-glucan from C. albicans (the primary β-glucan used in mouse and human studies) primed porcine monocytes for increased cytokine production after LPS and Pam 3 CSK 4 stimulation, an indication of trained immunity. Epigenetic analysis of the accessibility of the genome to transposase (ATAC-sequencing) showed changes in promoter peaks with treatment, providing insight into mechanisms of tolerance versus training. These data indicate that β-glucan can induce both training and tolerance in porcine monocytes, but the source and purity of β-glucan likely impacts innate memory.