Peroxisome-Mediated Metabolism Is Required for Immune Response to Microbial Infection
Peroxisome-Mediated Metabolism Is Required for Immune Response to Microbial Infection
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DOI：
10.1016/j.immuni.2017.06.016
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发表时间：
2017-07-18
期刊：
影响因子：
32.4
通讯作者：
Simmonds, Andrew J.
中科院分区：
文献类型：
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作者：
Di Cara, Francesca;Sheshachalam, Avinash;Simmonds, Andrew J.
先天免疫反应是动物体内平衡的关键，从无脊椎动物到脊椎动物都是保守的。这种反应依赖于通过吞噬作用识别、内化和摧毁微生物入侵者的特殊细胞。这与通过活性氧(ROS)和细胞因子产生的自主或非自主细胞信号相耦合。脂质是这一过程中已知的信号因素，因为巨噬细胞的急性期反应伴随着全身性脂质变化，有助于化解炎症。我们发现，过氧化体是果蝇和小鼠巨噬细胞吞噬细菌所必需的，它是脂质代谢和ROS转化的中心的膜封闭细胞器。通过规范的先天免疫信号解决细菌感染也需要过氧化物酶体。过氧酶体功能降低会损害抵抗感染所需的氧化爆发的周转。这种对细菌攻击的反应受损，影响了细胞和生物体的生存，揭示了以前未知的吞噬和天然免疫中对过氧化物酶体的要求。
The innate immune response is critical for animal homeostasis and is conserved from invertebrates to vertebrates. This response depends on specialized cells that recognize, internalize, and destroy microbial invaders through phagocytosis. This is coupled to autonomous or non-autonomous cellular signaling via reactive oxygen species (ROS) and cytokine production. Lipids are known signaling factors in this process, as the acute phase response of macrophages is accompanied by systemic lipid changes that help resolve inflammation. We found that peroxisomes, membrane-enclosed organelles central to lipid metabolism and ROS turnover, were necessary for the engulfment of bacteria by Drosophila and mouse macrophages. Peroxisomes were also required for resolution of bacterial infection through canonical innate immune signaling. Reduced peroxisome function impaired the turnover of the oxidative burst necessary to fight infection. This impaired response to bacterial challenge affected cell and organism survival and revealed a previously unknown requirement for peroxisomes in phagocytosis and innate immunity.