Cell Host & Micro：Chi3l1是一种保护机体免疫系统的关键蛋白

机体中的蛋白质对于维持机体对细菌的免疫反应至关重要，而且部分蛋白质可以保护机体免于自身的免疫效应伤害。近日来自耶鲁大学的研究者研究了一种名为壳多糖酶3（Chi3l1）的一种蛋白质，因为这种蛋白质是存在于植物、昆虫以及人类机体中的一种古老家族的蛋白质。进化上的保守性使得科学家认为Chi3l1在生物机体中扮演着重要的角色。然而目前对于Chi3l1的研究非常之少。

研究小组研究发现，当小鼠缺乏这种蛋白质并且暴露于肺炎链球菌的环境中时，小鼠机体中的炎症水平会大幅提高，机体会出现大幅的炎症损伤和出血情况，而且相比含有正常Chi3l1的蛋白质的小鼠来说，其致死率更高。研究者表示，这种蛋白质可以帮助巨噬细胞清理机体中的病原菌。相关研究成果刊登在了国际著名杂志Cell Host & Microbe上。

研究者同时发现Chi3l1可以抑制先天性免疫效应，并且可以降低其损伤宿主组织的能力。近些年来，科学家们对于经典免疫系统应答的领域越来越兴趣，研究者Charles表示，尤其是对于只清楚机体细菌而不杀伤机体的经典免疫系统应答领域，科学家们更为关注。他们发现的分子或许可以帮助机体达到这种免疫平衡效应。

编译自：Scientists pinpoint key ingredient in fighting pneumonia

doi:10.1016/j.chom.2012.05.017
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Chitinase 3-like-1 Promotes Streptococcus pneumoniae Killing and Augments Host Tolerance to Lung Antibacterial Responses

Charles S. Dela Cruz, Wei Liu, Chuan Hua He, Adam Jacoby, Alex Gornitzky, Bing Ma, Richard Flavell, Chun Geun Lee, Jack A. Elias

Host antibacterial responses include mechanisms that kill bacteria, but also those that protect or tolerize the host to potentially damaging antibacterial effects. We determined that Chitinase 3-like-1 (Chi3l1), a conserved prototypic chitinase-like protein, is induced by Streptococcus pneumoniae and plays central roles in promoting bacterial clearance and mediating host tolerance. S. pneumoniae-infected Chi3l1 null mice exhibit exaggerated lung injury, inflammation and hemorrhage, more frequent bacterial dissemination, decreased bacterial clearance, and enhanced mortality compared to controls. Chi3l1 augments macrophage bacterial killing by inhibiting caspase-1-dependent macrophage pyroptosis and augments host tolerance by controlling inflammasome activation, ATP accumulation, expression of ATP receptor P2X7R, and production of thymic stromal lymphopoietin and type 1, type 2, and type 17 cytokines. These data demonstrate that Chi3l1 is induced during infection, where it promotes bacterial clearance while simultaneously augmenting host tolerance, and that these roles likely contributed to the retention of Chi3l1 over species and evolutionary time.