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》。
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
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