Research on the metabolic immune regulation of macrophages by melanized fungus Fonsecaea monophora

Here, we evaluated the effects of Fonsecaea monophora（F. monophora）wild strain and the pigment knockout strain ΔpksA mutant on glucose metabolism and immune response of macrophages. The F. monophora wild strain significantly inhibited the glucose consumption level of macrophages or classically activated macrophages, and significantly inhibited the mRNA and protein expression levels of the tricarboxylic acid cycle gene IDH1 in macrophages. F. monophora wild strain inhibited the expression of pro-inflammatory cytokine IL-1β in macrophages, and up-regulated the expression of TNF and IL-6. The inhibition of glucose metabolism by 2-deoxy-d-glucose (2-DG) or metformin would affect the immune response of macrophages to F. monophora wild strain. The production of IL-1β in macrophages was significantly down-regulated, while the expression of TNF and IL-6 was not significantly affected. The ΔpksA saved the inhibitory effect of wild strains on glucose utilization in macrophages. Compared with wild strains, macrophages infected withΔpksA had higher glucose utilization levels and higher mRNA expression of IDH1. F. monophora wild strain inhibited IL-1β expression in macrophages, while ΔpksA promoted it. The expression of TNF and IL-6 in macrophages infected with ΔpksA was also significantly higher than that in the wild strain group.