TNF and type I IFN induction of the IRG1-itaconate pathway restricts Coxiella burnetii replication within mouse macrophages.
TNF and type I IFN induction of the IRG1-itaconate pathway restricts Coxiella burnetii replication within mouse macrophages.
复制标题
IRG1-衣康酸途径的 TNF 和 I 型 IFN 诱导限制了小鼠巨噬细胞内伯氏柯克斯体的复制。
DOI：
10.1101/2023.07.07.548079
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Shin,Sunny
中科院分区：
文献类型：
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作者：
Boyer,MarkA;Fischer,NatashaLopes;Shin,Sunny
细胞内的革兰氏阴性细菌贝氏柯克斯体在巨噬细胞内复制，并引起一种称为Q热的人畜共患疾病。在小鼠巨噬细胞中，细胞因子肿瘤坏死因子（TNF）对于限制细胞内C。贝氏复制在这里，我们表明，TNF与I型干扰素（IFN）信号合作，以最大限度地控制C。伯内特氏菌我们发现TNF和I型IFN上调代谢酶免疫应答基因1（IRG 1）的表达，也称为顺乌头酸脱羧酶1（ACOD 1），并且IRG 1是限制C.巨噬细胞内的贝氏T4 SS易位和复制。此外，我们还发现IRG 1的代谢产物衣康酸限制了C。贝氏体在细胞内和无菌培养中均能复制。这些数据表明，TNF和I型IFN上调IRG 1-衣康酸途径，以限制细胞内C。鼠巨噬细胞内的伯氏体复制。
The intracellular Gram-negative bacterium Coxiella burnetii replicates within macrophages and causes a zoonotic disease known as Q fever. In murine macrophages, the cytokine tumor necrosis factor (TNF) is critical for restriction of intracellular C. burnetii replication. Here, we show that TNF collaborates with type I interferon (IFN) signaling for maximal control of C. burnetii. We found that TNF and type I IFN upregulate the expression of the metabolic enzyme immune responsive gene 1 (IRG1), also known as cis-aconitate decarboxylase 1 (ACOD1), and that IRG1 is required to restrict C. burnetii T4SS translocation and replication within macrophages. Further, we show that itaconic acid, the metabolic product of IRG1, restricts C. burnetii replication both intracellularly and in axenic culture. These data reveal that TNF and type I IFN upregulate the IRG1-itaconate pathway to restrict intracellular C. burnetii replication within murine macrophages.