Local Necrotic Cells Trigger Systemic Immune Activation via Gut Microbiome Dysbiosis in Drosophila
Local Necrotic Cells Trigger Systemic Immune Activation via Gut Microbiome Dysbiosis in Drosophila
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DOI：
10.1016/j.celrep.2020.107938
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发表时间：
2020-07-21
期刊：
影响因子：
8.8
通讯作者：
Obata, Fumiaki
中科院分区：
文献类型：
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作者：
Kosakamoto, Hina;Yamauchi, Toshitaka;Obata, Fumiaki
坏死细胞通过其具有损伤相关分子模式的内源性因子引起炎症反应。阻断果蝇翅膀中的细胞凋亡通过未知机制导致坏死驱动的全身免疫应答。在这里，我们证明，免疫激活响应坏死细胞介导的肠道微生物群。去除微生物组减弱了坏死诱导的苍蝇中先天免疫信号转导IMD途径的过度激活。翅膀中的坏死细胞触发肠道中的葡萄糖酸盐扩张。分离的葡糖杆菌属（Gluconobactersp.）菌株足以在坏死诱导的苍蝇中进行病理性IMD激活，而其对于对照动物不是炎性的。此外，细菌定殖改变宿主代谢组，缩短坏死诱导的苍蝇的寿命。这项研究表明，局部坏死通过宿主与肠道微生物群之间的相互作用引发病理性全身炎症反应。
Necrotic cells elicit an inflammatory response through their endogenous factors with damage-associated molecular patterns. Blocking apoptosis in Drosophila wings leads to the necrosis-driven systemic immune response by unknown mechanisms. Here, we demonstrate that immune activation in response to necrotic cells is mediated by commensal gut microbiota. Removing the microbiome attenuates hyperactivation of the innate immune signaling IMD pathway in necrosis-induced flies. Necrotic cells in wings trigger Gluconobacter expansion in the gut. An isolated Gluconobactersp. strain is sufficient for pathological IMD activation in necrosis-induced flies, while it is not inflammatory for control animals. In addition, bacterial colonization shifts the host metabolome and shortens the lifespan of necrosis-induced flies. This study shows that local necrosis triggers a pathological systemic inflammatory response through interaction between the host and the dysbiotic gut microbiome.