Peritoneal tissue-resident macrophages are metabolically poised to engage microbes using tissue-niche fuels.
Peritoneal tissue-resident macrophages are metabolically poised to engage microbes using tissue-niche fuels.
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DOI：
10.1038/s41467-017-02092-0
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发表时间：
2017-12-12
影响因子：
16.6
通讯作者：
McVicar DW
中科院分区：
文献类型：
--
作者：
Davies LC;Rice CM;Palmieri EM;Taylor PR;Kuhns DB;McVicar DW
已经报道了代谢在巨噬细胞功能中的重要性，但体外观察结果的体内相关性仍不清楚。在这里，我们表明，巨噬细胞代谢物是在一个特定的组织背景下定义的，这些代谢物是至关重要的组织驻留巨噬细胞功能。我们发现腹膜富含谷氨酸盐，这是一种氨解燃料，腹膜驻留巨噬细胞通过增强线粒体复合物II代谢在吞噬过程中利用谷氨酸盐来维持呼吸爆发。这种小生境支持的、可诱导的线粒体功能依赖于蛋白激酶C活性，并且是微调控制炎症的细胞因子反应所必需的。此外，我们发现，腹膜驻留的巨噬细胞线粒体被招募到吞噬体，并产生来源于尿道的活性氧，这是杀死微生物所必需的。我们建议，组织驻留的巨噬细胞在原位代谢平衡，以保护和利用他们的组织生态位，利用当地可用的燃料来实施特定的代谢程序后，微生物传感。组织中的巨噬细胞既有一般的功能，也有组织特异性的功能，但后者的功能是如何灌输的还不清楚。在这里，作者表明，腹腔巨噬细胞表达一种专门的遗传程序，以利用局部富集的谷氨酸盐进行代谢，促进保护性原位免疫。
The importance of metabolism in macrophage function has been reported, but the in vivo relevance of the in vitro observations is still unclear. Here we show that macrophage metabolites are defined in a specific tissue context, and these metabolites are crucially linked to tissue-resident macrophage functions. We find the peritoneum to be rich in glutamate, a glutaminolysis-fuel that is exploited by peritoneal-resident macrophages to maintain respiratory burst during phagocytosis via enhancing mitochondrial complex-II metabolism. This niche-supported, inducible mitochondrial function is dependent on protein kinase C activity, and is required to fine-tune the cytokine responses that control inflammation. In addition, we find that peritoneal-resident macrophage mitochondria are recruited to phagosomes and produce mitochondrially derived reactive oxygen species, which are necessary for microbial killing. We propose that tissue-resident macrophages are metabolically poised in situ to protect and exploit their tissue-niche by utilising locally available fuels to implement specific metabolic programmes upon microbial sensing. Tissue-resident marcophages have both generic and tissue-specific functions, but how the latter functions are imbued is still unclear. Here the authors show that peritoneal macrophages express a specialised genetic programme to utilise the locally enriched glutamate for a metabolic setting that facilitates protective in situ immunity.
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影响因子：
7.4
作者：
Dikalov, Sergey
通讯作者：
Dikalov, Sergey
影响因子：
6.4
作者：
Davies LC;Taylor PR
通讯作者：
Taylor PR
DOI：
10.1152/ajpheart.1998.274.1.h342
发表时间：
1998-01-01
影响因子：
4.8
作者：
Chang, CI;Liao, JC;Kuo, L
通讯作者：
Kuo, L
影响因子：
15.9
作者：
Dillon, S;Agrawal, S;Pulendran, B
通讯作者：
Pulendran, B
影响因子：
64.5
作者：
Gosselin D;Link VM;Romanoski CE;Fonseca GJ;Eichenfield DZ;Spann NJ;Stender JD;Chun HB;Garner H;Geissmann F;Glass CK
通讯作者：
Glass CK