Monocytes maintain central nervous system homeostasis following helminth-induced inflammation.
Monocytes maintain central nervous system homeostasis following helminth-induced inflammation.
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DOI：
10.1073/pnas.2201645119
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发表时间：
2022-09-13
影响因子：
11.1
通讯作者：
Siracusa, Mark C.
中科院分区：
文献类型：
--
作者：
Peng, Jianya;Sy, Chandler B.;Ponessa, John J.;Lemenze, Alexander D.;Hernandez, Christina M.;Inclan-Rico, Juan M.;Sawhney, Arman;Federman, Hannah G.;Chavan, Krupa;Espinosa, Vanessa;Kotenko, Sergei V.;Rivera, Amariliz;Siracusa, Mark C.
神经免疫网络在协调宿主对不同病原体的防御方面发挥着至关重要的作用。此外，越来越多的文献表明，神经免疫串扰限制了免疫细胞的激活，从而促进了周围组织的完整性。然而，这是否是一个双向过程，免疫细胞是否通过调节中枢神经系统(CNS)的炎症反应和动态平衡发挥着类似的作用，目前仍不清楚。在这里，我们报告了蠕虫诱导的2型炎症促进了大脑中单核细胞的反应，这是抑制过度的小胶质细胞激活和宿主死亡所必需的。这项工作定义了在外周炎症的背景下，渗透的单核细胞促进中枢神经系统动态平衡的能力，并强调了神经免疫相互作用的双向和以前未被认识的方面。神经免疫相互作用对于调节免疫和炎症是至关重要的。最近的研究表明，中枢神经系统(CNS)感知外周炎症，并通过释放限制免疫细胞激活的分子来做出反应，从而促进耐受性和组织完整性。然而，这在多大程度上是一个双向的过程，以及外周免疫细胞是否也促进中枢神经系统的耐受机制仍然没有明确的定义。在这里，我们报告了蠕虫诱导的2型炎症促进了大脑中单核细胞的反应，这是抑制过度的小胶质细胞激活和宿主死亡所必需的。从机制上讲，感染诱导的单核细胞表达YM1，足以抑制激活的小胶质细胞产生肿瘤坏死因子。重要的是，神经保护性单核细胞持续存在于大脑中，在感染诱导的炎症消退几个月后，感染的小鼠可以免受随后的脂多糖诱导的神经炎症的影响。这些研究表明，渗入的单核细胞促进中枢神经系统的动态平衡，以响应外周的炎症，并证明外周感染可以改变宿主大脑的免疫格局。
Neuroimmune networks play critically important roles in coordinating host defense to diverse pathogens. Furthermore, a growing body of literature suggests that neuroimmune cross-talk limits immune cell activation and thereby promotes the integrity of peripheral tissues. However, whether this is a bidirectional process and immune cells play similar roles by regulating inflammatory responses and homeostasis in the central nervous system (CNS) remains poorly defined. Here we report that helminth-induced type 2 inflammation promotes monocyte responses in the brain that are required to inhibit excessive microglial activation and host death. This work defines the ability of infiltrating monocytes to promote CNS homeostasis in the context of peripheral inflammation and highlights bidirectional and previously unappreciated aspects of neuroimmune cross-talk. Neuroimmune interactions are crucial for regulating immunity and inflammation. Recent studies have revealed that the central nervous system (CNS) senses peripheral inflammation and responds by releasing molecules that limit immune cell activation, thereby promoting tolerance and tissue integrity. However, the extent to which this is a bidirectional process, and whether peripheral immune cells also promote tolerance mechanisms in the CNS remains poorly defined. Here we report that helminth-induced type 2 inflammation promotes monocyte responses in the brain that are required to inhibit excessive microglial activation and host death. Mechanistically, infection-induced monocytes express YM1 that is sufficient to inhibit tumor necrosis factor production from activated microglia. Importantly, neuroprotective monocytes persist in the brain, and infected mice are protected from subsequent lipopolysaccharide-induced neuroinflammation months after infection-induced inflammation has resolved. These studies demonstrate that infiltrating monocytes promote CNS homeostasis in response to inflammation in the periphery and demonstrate that a peripheral infection can alter the immunologic landscape of the host brain.
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DOI：
10.1084/jem.20111020
发表时间：
2011-11-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Braun TP;Zhu X;Szumowski M;Scott GD;Grossberg AJ;Levasseur PR;Graham K;Khan S;Damaraju S;Colmers WF;Baracos VE;Marks DL
通讯作者：
Marks DL
DOI：
10.4049/jimmunol.1200691
发表时间：
2012-11-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Giacomin PR;Siracusa MC;Walsh KP;Grencis RK;Kubo M;Comeau MR;Artis D
通讯作者：
Artis D
DOI：
10.1038/s41577-020-0301-x
发表时间：
2020-10
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
3.7
作者：
Brohawn, David G.;O'Brien, Laura C.;Bennett, James P., Jr.
通讯作者：
Bennett, James P., Jr.