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干扰素介导的膜胆固醇重编程逃避细菌毒素
作者:小柯机器人 发布时间:2020/6/11 11:16:06

美国加州大学洛杉矶分校Steven J. Bensinger团队发现,干扰素介导的膜胆固醇重编程逃避细菌毒素。该研究于2020年6月8日发表于《自然—免疫学》。

研究人员发现,干扰素(IFN)为巨噬细胞和中性粒细胞提供抵抗胆固醇依赖性细胞溶素(CDC)引起的打孔。研究人员发现巨噬细胞质膜中特定胆固醇池的快速调节影响IFN介导的CDC抗性,而没有改变总胆固醇水平。CDC引起的打孔抗性需要氧固醇25-羟基胆固醇(25HC)的产生,胆固醇合成的抑制以及胆固醇向酯化胆固醇池的重新分布。
 
因此,阻断IFN重新编程胆固醇代谢的能力使得细胞保护失效,并使小鼠更容易受到CDC诱导的组织损伤。这些研究表明,靶向调节膜胆固醇的含量可作为宿主防御策略。
 
据了解,动物细胞的质膜富含胆固醇。CDC是由细菌分泌的打孔毒素,这些毒素靶向膜胆固醇来发挥其效应子功能。吞噬细胞对于清除产生CDC的细菌至关重要。然而,这些细胞逃避CDC有害作用的机制尚不清楚。
 
附:英文原文

Title: Interferon-mediated reprogramming of membrane cholesterol to evade bacterial toxins

Author: Quan D. Zhou, Xun Chi, Min Sub Lee, Wei Yuan Hsieh, Jonathan J. Mkrtchyan, An-Chieh Feng, Cuiwen He, Autumn G. York, Viet L. Bui, Eliza B. Kronenberger, Alessandra Ferrari, Xu Xiao, Allison E. Daly, Elizabeth J. Tarling, Robert Damoiseaux, Philip O. Scumpia, Stephen T. Smale, Kevin J. Williams, Peter Tontonoz, Steven J. Bensinger

Issue&Volume: 2020-06-08

Abstract: Plasma membranes of animal cells are enriched for cholesterol. Cholesterol-dependent cytolysins (CDCs) are pore-forming toxins secreted by bacteria that target membrane cholesterol for their effector function. Phagocytes are essential for clearance of CDC-producing bacteria; however, the mechanisms by which these cells evade the deleterious effects of CDCs are largely unknown. Here, we report that interferon (IFN) signals convey resistance to CDC-induced pores on macrophages and neutrophils. We traced IFN-mediated resistance to CDCs to the rapid modulation of a specific pool of cholesterol in the plasma membrane of macrophages without changes to total cholesterol levels. Resistance to CDC-induced pore formation requires the production of the oxysterol 25-hydroxycholesterol (25HC), inhibition of cholesterol synthesis and redistribution of cholesterol to an esterified cholesterol pool. Accordingly, blocking the ability of IFN to reprogram cholesterol metabolism abrogates cellular protection and renders mice more susceptible to CDC-induced tissue damage. These studies illuminate targeted regulation of membrane cholesterol content as a host defense strategy.

DOI: 10.1038/s41590-020-0695-4

Source: https://www.nature.com/articles/s41590-020-0695-4

期刊信息

Nature Immunology:《自然—免疫学》,创刊于2000年。隶属于施普林格·自然出版集团,最新IF:23.53
官方网址:https://www.nature.com/ni/
投稿链接:https://mts-ni.nature.com/cgi-bin/main.plex