中文摘要：

神經(jīng)免疫相互作用對(duì)于調(diào)節(jié)免疫和炎癥至關(guān)重要。近期研究表明，中樞神經(jīng)系統(tǒng)（CNS）能夠感知外周炎癥，并通過釋放分子來限制免疫細(xì)胞活化，從而促進(jìn)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(xì)胞是否也能促進(jìn)中樞神經(jīng)系統(tǒng)內(nèi)的耐受機(jī)制，目前仍知之甚少。

本研究發(fā)現(xiàn)，蠕蟲感染誘導(dǎo)的2型炎癥可促進(jìn)腦內(nèi)單核細(xì)胞反應(yīng)，而這種反應(yīng)對(duì)于抑制過度的膠質(zhì)細(xì)胞激活和宿主死亡是必需的。在機(jī)制上，感染誘導(dǎo)的單核細(xì)胞表達(dá)YM1分子，該分子足以抑制活化的小膠質(zhì)細(xì)胞產(chǎn)生腫瘤壞死因子（TNF）。重要的是，這些神經(jīng)保護(hù)性單核細(xì)胞在腦內(nèi)持續(xù)存在，且在感染誘發(fā)的炎癥消退數(shù)月后，曾感染的小鼠仍能免受后續(xù)脂多糖（LPS）誘導(dǎo)的神經(jīng)炎癥損傷。

這些研究表明，浸潤(rùn)的單核細(xì)胞能夠響應(yīng)外周炎癥而促進(jìn)中樞神經(jīng)系統(tǒng)穩(wěn)態(tài)，同時(shí)也證明外周感染可以改變宿主大腦的免疫微環(huán)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(shí)間期卷：119 (37) e2201645119

DOI: 10.1073/pnas.2201645119

產(chǎn)品信息：

貨號(hào)：CP-010-010

規(guī)格：10ml+10ml

品牌：Liposoma

產(chǎn)地：荷蘭

名稱：Clodronate Liposomes&Control Liposomes

辦事處：靶點(diǎn)科技

Clodronate Liposomes氯膦酸鹽脂質(zhì)體外周血單核巨噬細(xì)胞。荷蘭Liposoma巨噬細(xì)胞清除劑ClodronateLiposomes見刊于PNAS：單核細(xì)胞在蠕蟲誘導(dǎo)的炎癥后維持中樞神經(jīng)系統(tǒng)穩(wěn)態(tài)。

Liposoma巨噬細(xì)胞清除劑Clodronate Liposomes氯膦酸二鈉脂質(zhì)體清除巨噬細(xì)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(xì)胞清除材料和方法文獻(xiàn)截圖：