Legionella-Infected Macrophages Engage the Alveolar Epithelium to Metabolically Reprogram Myeloid Cells and Promote Antibacterial Inflammation.
Legionella-Infected Macrophages Engage the Alveolar Epithelium to Metabolically Reprogram Myeloid Cells and Promote Antibacterial Inflammation.
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DOI：
10.1016/j.chom.2020.07.019
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发表时间：
2020-11-11
影响因子：
30.3
通讯作者：
Shin, Sunny
中科院分区：
文献类型：
--
作者：
Liu, Xin;Boyer, Mark A.;Holmgren, Alicia M.;Shin, Sunny
肺泡巨噬细胞是对吸入的病原体作出反应的第一批免疫细胞之一。然而，许多病原体阻断巨噬细胞的内在免疫反应，使其不清楚如何产生强大的抗菌反应。细胞内细菌嗜肺军团菌抑制宿主翻译，从而削弱受感染的巨噬细胞产生细胞因子。然而，军团菌感染的巨噬细胞通过募集的单核细胞和其他控制感染的细胞诱导IL-1依赖性炎性细胞因子应答。IL-1如何指导这些细胞产生炎性细胞因子尚不清楚。在这里，我们表明，与肺泡上皮细胞的合作是控制感染的关键。IL-1诱导肺泡上皮细胞产生粒细胞-巨噬细胞集落刺激因子（GM-CSF）。有趣的是，GM-CSF信号通过增强TLR诱导的糖酵解来放大募集的单核细胞中的炎性细胞因子产生。我们的研究结果表明，肺泡巨噬细胞参与肺泡上皮细胞的信号代谢重组单核细胞抗菌炎症。Xin等人表明，在肺部细菌感染期间，肺泡上皮细胞能够在受感染的肺泡巨噬细胞和募集的骨髓细胞之间进行通信。从机制上讲，感染的巨噬细胞释放的IL-1诱导肺泡上皮细胞产生GM-CSF。GM-CSF反过来代谢重编程单核细胞，放大炎症反应并促进宿主防御。
Alveolar macrophages are among the first immune cells that respond to inhaled pathogens. However, numerous pathogens block macrophage-intrinsic immune responses, making it unclear how robust antimicrobial responses are generated. The intracellular bacterium Legionella pneumophila inhibits host translation, thereby impairing cytokine production by infected macrophages. Nevertheless, Legionellainfected macrophages induce an IL-1-dependent inflammatory cytokine response by recruited monocytes and other cells that controls infection. How IL-1 directs these cells to produce inflammatory cytokines is unknown. Here, we show that collaboration with the alveolar epithelium is critical for controlling infection. IL-1 induces the alveolar epithelium to produce granulocyte-macrophage colony-stimulating factor (GM-CSF). Intriguingly, GM-CSF signaling amplifies inflammatory cytokine production in recruited monocytes by enhancing TLR-induced glycolysis. Our findings reveal that alveolar macrophages engage alveolar epithelial signals to metabolically reprogram monocytes for antibacterial inflammation. Xin et al. show that the alveolar epithelium enables communication between infected alveolar macrophages and recruited myeloid cells during pulmonary bacterial infection. Mechanistically, IL-1 released by infected macrophages induces the alveolar epithelium to produce GM-CSF. GM-CSF in turn metabolically reprograms monocytes, amplifying inflammatory responses and promoting host defense.
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影响因子：
64.5
作者：
Chang CH;Curtis JD;Maggi LB Jr;Faubert B;Villarino AV;O'Sullivan D;Huang SC;van der Windt GJ;Blagih J;Qiu J;Weber JD;Pearce EJ;Jones RG;Pearce EL
通讯作者：
Pearce EL
影响因子：
3.1
作者：
Brieland, JK;Remick, DG;Fantone, JC
通讯作者：
Fantone, JC
影响因子：
32.4
作者：
Croxford, Andrew L.;Lanzinger, Margit;Becher, Burkhard
通讯作者：
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影响因子：
6.7
作者：
Asrat S;Dugan AS;Isberg RR
通讯作者：
Isberg RR
影响因子：
56.9
作者：
DRANOFF, G;CRAWFORD, AD;MULLIGAN, RC
通讯作者：
MULLIGAN, RC