中文摘要：

目前支撐作用，關(guān)于全身性感染引發(fā)膿毒癥中過度炎癥反應(yīng)和免疫功能障礙的機(jī)制尚不清楚研學體驗。細(xì)胞外組蛋白會(huì)加劇膿毒癥病理進(jìn)程，但其來源和作用機(jī)制仍不明確。本研究揭示落實落細，中性粒細(xì)胞來源的髓過氧化物酶通過抑制組蛋白釋放相結合，在調(diào)控脾巨噬細(xì)胞捕獲的真菌和細(xì)菌過程中發(fā)揮膿毒癥緩解作用。在系統(tǒng)性念珠菌感染中製高點項目，吞噬受體SIGNR1介導(dǎo)的微生物捕獲通過促進(jìn)邊緣區(qū)浸潤(rùn)和T細(xì)胞死亡依賴性組蛋白釋放為產業發展，中和了髓過氧化物酶活性。組蛋白和菌絲可誘導(dǎo)鄰近CD169+巨噬細(xì)胞產(chǎn)生細(xì)胞因子（包括G-CSF）有所增加，這些因子通過縮短成熟Ly6G高表達(dá)中性粒細(xì)胞的存活時(shí)間各項要求，選擇性耗竭該類細(xì)胞，轉(zhuǎn)而促進(jìn)具有氧化爆發(fā)缺陷的未成熟Ly6G低表達(dá)中性粒細(xì)胞存活估算。在膿毒癥患者血漿中講理論，這些介質(zhì)可縮短成熟中性粒細(xì)胞壽命，并與中性粒細(xì)胞死亡標(biāo)志物相關(guān)不要畏懼。因此服務為一體，高G-CSF水平和中性粒細(xì)胞壽命縮短活性與膿毒癥患者死亡率密切相關(guān)。綜上逐漸顯現，病原體通過利用吞噬受體全會精神，借助下游效應(yīng)因子對(duì)中性粒細(xì)胞壽命的有害影響，削弱了先天性和適應(yīng)性免疫功能拓展基地。

英文摘要：

The mechanisms linking systemic infection to hyperinflammation and immune dysfunction in sepsis are poorly understood. Extracellular histones promote sepsis pathology, but their source and mechanism of action remain unclear. Here, we show that by controlling fungi and bacteria captured by splenic macrophages, neutrophil-derived myeloperoxidase attenuates sepsis by suppressing histone release. In systemic candidiasis, microbial capture via the phagocytic receptor SIGNR1 neutralizes myeloperoxidase by facilitating marginal zone infiltration and T cell death-dependent histone release. Histones and hyphae induce cytokines in adjacent CD169 macrophages including G-CSF that selectively depletes mature Ly6Ghigh neutrophils by shortening their lifespan in favour of immature Ly6Glow neutrophils with a defective oxidative burst. In sepsis patient plasma, these mediators shorten mature neutrophil lifespan and correlate with neutrophil mortality markers. Consequently, high G-CSF levels and neutrophil lifespan shortening activity are associated with sepsis patient mortality. Hence, by exploiting phagocytic receptors, pathogens degrade innate and adaptive immunity through the detrimental impact of downstream effectors on neutrophil lifespan.

論文信息：

論文題目：

Microbe capture by splenic macrophages triggers sepsis via T cell-death-dependent neutrophil lifespan shortening

期刊名稱：Nature Communications

時(shí)間期卷：13, Article number: 4658 (2022)

在線時(shí)間：2022年8月9日

DOI：doi.org/10.1038/s41467-022-32320-1

產(chǎn)品信息：

貨號(hào)：CP-005-005

規(guī)格：5ml+5ml

品牌：Liposoma

產(chǎn)地：荷蘭

名稱：Clodronate Liposomes and Control Liposomes

辦事處：Target Technology（靶點(diǎn)科技）

氯膦酸鹽脂質(zhì)體清除脾臟巨噬細(xì)胞在膿毒血癥模型中心粒細(xì)胞功能研究集中展示，荷蘭Liposoma巨噬細(xì)胞清除劑Clodronate Liposomes見刊于Nature Communications：

氯膦酸二鈉脂質(zhì)體清除巨噬細(xì)胞助力脾臟膿毒癥模型免疫研究

Liposoma巨噬細(xì)胞清除劑Clodronate Liposomes氯膦酸二鈉脂質(zhì)體的材料和方法：

Induction of peripheral Ly6Glow neutrophils in na?ve mice

Mice were injected intravenously with 1?mg of Clo-L or PBS-L (Liposoma) and the subsequent day intraperitoneally with 2.5?μg rG-CSF (BioLegend) or vehicle (PBS). Analysis of neutrophil populations was performed 2?days after rG-CSF injection, according to the methods described in flow cytometric analysis.

Neutrophil and macrophage depletion in vivo

Neutrophil depletion was achieved with intraperitoneal injection of 150?μg anti-Ly6G Ab (BioXCell) or IgG isotype control (BioXCell) at day ?1 and day 0 (day of infection). Macrophage depletion was performed with intravenous administration of 1?mg Clodronate liposomes (Clo-L) or 1?mg PBS liposomes (PBS-L) as control (Liposoma) at 1?day prior to infection.