Abstract
Epigenetic reprogramming of innate immune cells by β-glucan in a process called trained immunity leads to an enhanced host response to a secondary infection. β-Glucans are structural components of plants, algae, fungi, and bacteria and thus recognized as non-self by human macrophages. We selected the β-glucan curdlan from Alcaligenes faecalis, WGP dispersible from Saccharomyces cerevisiae, and β-glucan-rich culture supernatant of Alternaria and investigated whether they could produce trained immunity effects leading to an increased control of virulent Mycobacterium tuberculosis. We observed a significant M. tuberculosis growth reduction in macrophages trained with curdlan and Alternaria, which also correlated with increased IL-6 and IL-1β release. WGP dispersible-trained macrophages were stratified into "non-responders" and "responders," according to their ability to control M. tuberculosis, with "responders" producing higher IL-6 levels. The addition of neutrophils to infected macrophage cultures further enhanced macrophage control of virulent M. tuberculosis, but not in a stimuli-dependent manner. Pathway enrichment analysis of DNA methylome data also highlighted hypomethylation of genes in pathways associated with signaling and cellular reorganization and motility, and "responders" to WGP training were enriched in the interferon-gamma signaling pathway. This study adds evidence that certain β-glucans show promise as immune-training agents.