The microbiota protects against respiratory infection via GM-CSF signaling.
The microbiota protects against respiratory infection via GM-CSF signaling.
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微生物群通过GM-CSF信号传导防止呼吸道感染。
DOI：
10.1038/s41467-017-01803-x
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发表时间：
2017-11-15
影响因子：
16.6
通讯作者：
Clarke TB
中科院分区：
文献类型：
--
作者：
Brown RL;Sequeira RP;Clarke TB
微生物群可促进对呼吸道感染的抵抗力，但其机制基础尚不清楚。在这里，我们确定了可预防主要人类病原体肺炎链球菌和肺炎克雷伯菌引起的呼吸道感染的微生物群成员。我们发现微生物群通过粒细胞-巨噬细胞集落刺激因子（GM-CSF）信号传导增强呼吸防御，该信号传导通过细胞外信号调节激酶信号传导刺激肺泡巨噬细胞杀死和清除病原体。微生物群通过白细胞介素 17A 引发肺部 GM-CSF 生成量的增加，以应对感染。通过结合抗生素治疗和无菌小鼠的共生定植模型，使用放线菌门、拟杆菌门、厚壁菌门和变形菌门的培养共生菌，我们发现上呼吸道（金黄色葡萄球菌和表皮葡萄球菌）和肠道微生物群（罗伊氏乳杆菌、肠球菌）中有效的 Nod 样受体刺激细菌粪杆菌、卷曲乳杆菌和Clostridium orbiscindens）通过Nod2和GM-CSF促进对肺部感染的抵抗力。我们的数据揭示了微生物群中调节肺部免疫力的细菌的身份、位置和特性，并描绘了它们激活以防止呼吸道感染的宿主信号轴。微生物群通过尚不清楚的机制促进对呼吸道感染的抵抗力。在这里，作者确定了肠道和上呼吸道微生物群的成员，它们通过激活 GM-CSF 信号传导来防止肺炎链球菌和肺炎克雷伯菌引起的呼吸道感染。
The microbiota promotes resistance to respiratory infection, but the mechanistic basis for this is poorly defined. Here, we identify members of the microbiota that protect against respiratory infection by the major human pathogens Streptococcus pneumoniae and Klebsiella pneumoniae. We show that the microbiota enhances respiratory defenses via granulocyte–macrophage colony-stimulating factor (GM-CSF) signaling, which stimulates pathogen killing and clearance by alveolar macrophages through extracellular signal-regulated kinase signaling. Increased pulmonary GM-CSF production in response to infection is primed by the microbiota through interleukin-17A. By combining models of commensal colonization in antibiotic-treated and germ-free mice, using cultured commensals from the Actinobacteria, Bacteroidetes, Firmicutes, and Proteobacteria phyla, we found that potent Nod-like receptor-stimulating bacteria in the upper airway (Staphylococcus aureus and Staphylococcus epidermidis) and intestinal microbiota (Lactobacillus reuteri, Enterococcus faecalis, Lactobacillus crispatus and Clostridium orbiscindens) promote resistance to lung infection through Nod2 and GM-CSF. Our data reveal the identity, location, and properties of bacteria within the microbiota that regulate lung immunity, and delineate the host signaling axis they activate to protect against respiratory infection. The microbiota promotes resistance to respiratory infection through unclear mechanisms. Here, the authors identify members of the gut and upper airway microbiota that protect against respiratory infection by Streptococcus pneumoniae and Klebsiella pneumoniae by activating GM-CSF signaling.
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影响因子：
30.3
作者：
Cahenzli J;Köller Y;Wyss M;Geuking MB;McCoy KD
通讯作者：
McCoy KD
影响因子：
17.1
作者：
Gray J;Oehrle K;Worthen G;Alenghat T;Whitsett J;Deshmukh H
通讯作者：
Deshmukh H
影响因子：
3.1
作者：
Gauguet, Stefanie;D'Ortona, Samantha;Pier, Gerald B.
通讯作者：
Pier, Gerald B.
DOI：
10.1073/pnas.1019378108
发表时间：
2011-03-29
影响因子：
11.1
作者：
Ichinohe, Takeshi;Pang, Iris K.;Iwasaki, Akiko
通讯作者：
Iwasaki, Akiko
影响因子：
64.8
作者：
Bouskra, Djahida;Brezillon, Christophe;Eberl, Gerard
通讯作者：
Eberl, Gerard