MDA5 Enhances Invasive Candida albicans Infection by Regulating Macrophage Apoptosis and Phagocytosis/Killing Functions
MDA5 Enhances Invasive Candida albicans Infection by Regulating Macrophage Apoptosis and Phagocytosis/Killing Functions
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DOI：
10.1007/s10753-023-01903-5
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发表时间：
2023-09
期刊：
影响因子：
5.1
通讯作者：
Yayun Chen;Qian Jiang;Furong Qing;Junxia Xue;Qiuxiang Xiao;Wenji He;Lina Sui;Zhiping Liu
中科院分区：
文献类型：
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作者：
Yayun Chen;Qian Jiang;Furong Qing;Junxia Xue;Qiuxiang Xiao;Wenji He;Lina Sui;Zhiping Liu
Candida albicansis a common opportunistic pathogenic fungus. The innate immune system provides the first-line host defense against fungal infection. Innate immune receptors and downstream molecules have been shown to play various roles during fungal infection.The innate immune receptor MDA5, encoded by the geneIfih1, enhances host resistance against viral andAspergillus fumigatusinfection by inducing the production of interferons (IFNs). However, the role of MDA5 inC. albicansinfection is still unclear. Here, we found that the gene expression levels ofIFIH1were significantly increased in innate immune cells afterC. albicansstimulation through human bioinformatics analysis or mouse experiments. Throughin vivostudy, MDA5 was shown to enhance host susceptibility toC. albicansinfection independent of IFN production. Instead, MDA5 exerted its influence on macrophages and kidneys by modulating the expression of Noxa, Bcl2, and Bax, thereby promoting apoptosis. Additionally, MDA5 compromised killing capabilities of macrophage by inhibition iNOS expression. The introduction of the apoptosis inducer PAC1 further impaired macrophage functions, mimicking the enhancing effect of MDA5 onC. albicansinfection. Furthermore, the administration of macrophage scavengers increased the susceptibility ofIfih1−/−mice toC. albicans. The founding suggests that MDA5 promote host susceptibility to invasiveC. albicansby enhancing cell apoptosis and compromising macrophage functions, making MDA5 a target to treatcandidiasis.
