中文摘要:
神經免疫相互作用對于調節免疫和炎癥至關重要。近期研究表明,中樞神經系統(CNS)能夠感知外周炎癥,并通過釋放分子來限制免疫細胞活化,從而促進免疫耐受和組織完整性。然而,這一過程在多大程度上是雙向的,以及外周免疫細胞是否也能促進中樞神經系統內的耐受機制,目前仍知之甚少。
本研究發現,蠕蟲感染誘導的2型炎癥可促進腦內單核細胞反應,而這種反應對于抑制過度的膠質細胞激活和宿主死亡是必需的。在機制上,感染誘導的單核細胞表達YM1分子,該分子足以抑制活化的小膠質細胞產生腫瘤壞死因子(TNF)。重要的是,這些神經保護性單核細胞在腦內持續存在,且在感染誘發的炎癥消退數月后,曾感染的小鼠仍能免受后續脂多糖(LPS)誘導的神經炎癥損傷。
這些研究表明,浸潤的單核細胞能夠響應外周炎癥而促進中樞神經系統穩態,同時也證明外周感染可以改變宿主大腦的免疫微環境。
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.
論文信息:
論文題目:Monocytes maintain central nervous system homeostasis following helminth-induced inflammation
期刊名稱:PNAS
時間期卷:119 (37) e2201645119
DOI: 10.1073/pnas.2201645119
產品信息:
貨號:CP-010-010
規格:10ml+10ml
品牌:Liposoma
產地:荷蘭
名稱:Clodronate Liposomes&Control Liposomes
辦事處:靶點科技
Clodronate Liposomes氯膦酸鹽脂質體外周血單核巨噬細胞。荷蘭Liposoma巨噬細胞清除劑ClodronateLiposomes見刊于PNAS:單核細胞在蠕蟲誘導的炎癥后維持中樞神經系統穩態。

Liposoma巨噬細胞清除劑Clodronate Liposomes氯膦酸二鈉脂質體清除巨噬細胞的材料和方法:
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.
巨噬細胞清除材料和方法文獻截圖:

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