中文摘要:
神经免疫相互作用对于调节免疫和炎症至关重要。近期研究表明,中枢神经系统(CNS)能够感知外周炎症,并通过释放分子来限制免疫细胞活化,从而促进免疫耐受和组织完整性。然而,这一过程在多大程度上是双向的,以及外周免疫细胞是否也能促进中枢神经系统内的耐受机制,目前仍知之甚少。
本研究发现,蠕虫感染诱导的2型炎症可促进脑内单核细胞反应,而这种反应对于抑制过度的胶质细胞激活和宿主死亡是必需的。在机制上,感染诱导的单核细胞表达YM1分子,该分子足以抑制活化的小胶质细胞产生肿瘤坏死因子(TNF)。重要的是,这些神经保护性单核细胞在脑内持续存在,且在感染诱发的炎症消退数月后,曾感染的小鼠仍能免受后续脂多糖(LPS)诱导的神经炎症损伤。
这些研究表明,浸润的单核细胞能够响应外周炎症而促进中枢神经系统稳态,同时也证明外周感染可以改变宿主大脑的免疫微环境。
英文摘要:
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.
论文信息:
论文题目:Monocytes maintain central nervous system homeostasis following helminth-induced inflammation
期刊名称:PNAS
时间期卷:119 (37) e2201645119
DOI: 10.1073/pnas.2201645119
产品信息:
货号:CP-010-010
规格:10ml+10ml
品牌:Liposoma
产地:荷兰
名称:Clodronate Liposomes&Control Liposomes
办事处:靶点科技
Clodronate Liposomes氯膦酸盐脂质体外周血单核巨噬细胞。荷兰Liposoma巨噬细胞清除剂ClodronateLiposomes见刊于PNAS:单核细胞在蠕虫诱导的炎症后维持中枢神经系统稳态。

Liposoma巨噬细胞清除剂Clodronate Liposomes氯膦酸二钠脂质体清除巨噬细胞的材料和方法:
In vivo macrophage depletion
For depletion of CCR2+ monocytes, CCR2-DTR mice and littermate controls were handled as published previously (34). The generalized depletion of macrophages and other phagocytic cells were executed based on the protocol from Liposoma. At necropsy, single-cell suspensions of mesenteric lymph nodes and spleens, and intestinal worm counts were processed as previously described (83). Whole blood was collected in BD Vacutainer Glass Blood Collection Tubes with K3 EDTA, and plasma was isolated for later analysis. Sections of brain, small intestine, kidney, liver, and gastrocnemius muscle were collected in RNAlater buffer for RT-qPCR analysis and formalin for histological analysis (H&E) and immunofluorescent microscopy. ImageJ (v1.52a) software was used to measure cross-sectional areas of muscle fibers from the gastrocnemius (84).
For the adoptive transfer of monocytes to monocyte-depleted animals, monocytes were isolated from infected WT mice bone marrow and spleen 2, 3, 4, 5, and 6 dpi, and then sort-purified. One to one and a half million cells were given to each DTR recipient through retro-orbital vein intravenous injection. Control animals received same volume of sterile PBS.
巨噬细胞清除材料和方法文献截图:
