此前已有研究證實(shí)，在蠕蟲感染背景下，有多種細(xì)胞和分子機(jī)制可促進(jìn)宿主耐受性，從而防止免疫病理損傷。其中包括M2型巨噬細(xì)胞的作用以及神經(jīng)免疫調(diào)節(jié)回路。盡管取得了這些進(jìn)展，但在全球傳播寄生蟲感染之一——旋毛蟲（T. spiralis）感染中，促進(jìn)耐受性的具體通路仍有待明確。因此，我們首先旨在研究旋毛蟲感染腸道期M2型巨噬細(xì)胞的作用。感染后第8天，小腸中M2相關(guān)標(biāo)志物Arg1、Retnla和Chil3的表達(dá)升高，提示存在感染誘導(dǎo)的M2型巨噬細(xì)胞（圖1A）。為評(píng)估巨噬細(xì)胞對(duì)宿主保護(hù)作用的貢獻(xiàn)，我們在感染后經(jīng)靜脈給予小鼠磷酸鹽緩沖液（PBS：P-005）或載有氯膦酸鹽（CL：C-005）的脂質(zhì)體，以清除多種髓系細(xì)胞群體。結(jié)果顯示，CL脂質(zhì)體處理確實(shí)耗竭了Ly6C+CD11b+單核細(xì)胞和F4/80+CD11b+巨噬細(xì)胞（圖1 B–E）。此外，CL脂質(zhì)體處理還導(dǎo)致小腸中感染誘導(dǎo)的Arg1、Retnla和Chil3表達(dá)喪失（圖1A）。無論P(yáng)BS還是CL處理，感染動(dòng)物間iNOS表達(dá)均無顯著變化（附錄圖S1A）。關(guān)鍵在于，接受CL脂質(zhì)體處理的小鼠較對(duì)照組體重下降更明顯，死亡率也更高（圖1 F和G）。上述數(shù)據(jù)表明，通過CL脂質(zhì)體遞送清除吞噬細(xì)胞會(huì)導(dǎo)致腸道內(nèi)感染誘導(dǎo)的M2型反應(yīng)喪失，并與宿主發(fā)病率和死亡率升高相關(guān)。

M2型巨噬細(xì)胞的缺失與旋毛蟲感染后發(fā)病率和死亡率的增加相關(guān)。經(jīng)靜脈注射磷酸鹽緩沖液（PBS）或載有氯膦酸鹽（CL）脂質(zhì)體的小鼠被旋毛蟲感染，并于感染后第8天處死。（A）通過RT-qPCR檢測腸道中M2相關(guān)標(biāo)志物的表達(dá)。（B和C）單核細(xì)胞（Ly6C+CD11b+）以及（D和E）巨噬細(xì)胞（F4/80+CD11b+）在脾臟中的存在與否通過流式細(xì)胞術(shù)測定。細(xì)胞群體從CD45hiCD3?CD19?Ly6G?細(xì)胞中設(shè)門圈出。流式細(xì)胞術(shù)圖中的數(shù)字代表CD45hi細(xì)胞的百分比。（F）在整個(gè)感染過程中監(jiān)測體重變化，（G）記錄死亡率。

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：