Metabolic immune regulation of macrophages by melanized fungus Fonsecaea monophora.

IF 1.8 4区医学 Q3 MYCOLOGY

Journal de mycologie medicale Pub Date : 2025-09-01 Epub Date: 2025-07-28 DOI:10.1016/j.mycmed.2025.101571

Qinling Pan, Tengteng Xin, Jing Zhang, Li Lin, Junmin Zhang

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引用次数: 0

Abstract

Background: Glucose metabolism in the host is crucial during microbial infections. 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.

Methods: Glucose consumption, lactate secretion, genes related to glucose metabolism, and pro-inflammatory cytokines were measured in mouse macrophage J774A.1 cells infected with F. monophora wild strain or ΔpksA. Notably, 2-deoxy-d-glucose (2-DG) and metformin (Glucophage) were used to inhibit glucose metabolism in macrophages.

Results: 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 (Glucophage) 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.

Conclusion: Our results suggest that F. monophora wild strain reduces IL-1β expression by inhibiting the IDH1-related tricarboxylic acid cycle in macrophages. F. monophora melanin is a fungal virulence factor that inhibits glucose metabolism and regulates the immune response of macrophages.

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黑化真菌对巨噬细胞代谢免疫的调节作用。

背景：在微生物感染过程中，宿主的葡萄糖代谢是至关重要的。在这里，我们评估了单核丰secaea monophora （F. monophora）野生菌株和色素敲除菌株ΔpksA突变株对巨噬细胞糖代谢和免疫反应的影响。方法：测定小鼠巨噬细胞J774A的葡萄糖消耗、乳酸分泌、糖代谢相关基因和促炎细胞因子。1细胞感染单孢单胞菌野生菌株或ΔpksA。值得注意的是，使用2-脱氧-d-葡萄糖（2-DG）和二甲双胍（Glucophage）抑制巨噬细胞的葡萄糖代谢。结果：单孢F. monophora野生菌株显著抑制巨噬细胞或经典活化巨噬细胞的葡萄糖消耗水平，显著抑制巨噬细胞三羧酸循环基因IDH1 mRNA和蛋白水平。野生菌株抑制巨噬细胞中促炎因子IL-1β的表达，上调TNF和IL-6的表达。2-DG或二甲双胍（Glucophage）抑制糖代谢影响巨噬细胞对单孢单胞菌野生菌株的免疫应答。巨噬细胞IL-1β的产生明显下调。与对照组相比，ΔpksA未改变巨噬细胞的葡萄糖利用和IDH1表达。F. monophora野生菌株抑制巨噬细胞中IL-1β的表达，ΔpksA促进IL-1β的表达。结论：野生单孢假单胞菌通过抑制idh1相关的三羧酸循环降低巨噬细胞IL-1β的表达。F. monophora melanin是一种真菌毒力因子，可抑制糖代谢，调节巨噬细胞的免疫反应。

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来源期刊

Journal de mycologie medicale 医学-真菌学

CiteScore

5.10

自引率

2.80%

发文量

审稿时长

6-12 weeks

期刊介绍： The Journal de Mycologie Medicale / Journal of Medical Mycology (JMM) publishes in English works dealing with human and animal mycology. The subjects treated are focused in particular on clinical, diagnostic, epidemiological, immunological, medical, pathological, preventive or therapeutic aspects of mycoses. Also covered are basic aspects linked primarily with morphology (electronic and photonic microscopy), physiology, biochemistry, cellular and molecular biology, immunochemistry, genetics, taxonomy or phylogeny of pathogenic or opportunistic fungi and actinomycetes in humans or animals. Studies of natural products showing inhibitory activity against pathogenic fungi cannot be considered without chemical characterization and identification of the compounds responsible for the inhibitory activity. JMM publishes (guest) editorials, original articles, reviews (and minireviews), case reports, technical notes, letters to the editor and information. Only clinical cases with real originality (new species, new clinical present action, new geographical localization, etc.), and fully documented (identification methods, results, etc.), will be considered. Under no circumstances does the journal guarantee publication before the editorial board makes its final decision. The journal is indexed in the main international databases and is accessible worldwide through the ScienceDirect and ClinicalKey platforms.