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 levels of the tricarboxylic acid cycle gene IDH1 in macrophages. F. monophora wild strain inhibited the expression of the pro-inflammatory cytokine IL-1β in macrophages, and upregulated the expression of TNF and IL-6. Inhibition of glucose metabolism by 2-DG or metformin affected the immune response of macrophages to F. monophora wild strain. The production of IL-1β in macrophages was significantly downregulated. Compared with the control group, ΔpksA did not change glucose utilization and IDH1 expression in macrophages. F. monophora wild strain inhibited IL-1β expression in macrophages, while ΔpksA promoted it.