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2 results on '"Chi, Xun"'

1. Interferon-mediated reprogramming of membrane cholesterol to evade bacterial toxins.

Author

Zhou QD, Chi X, Lee MS, Hsieh WY, Mkrtchyan JJ, Feng AC, He C, York AG, Bui VL, Kronenberger EB, Ferrari A, Xiao X, Daly AE, Tarling EJ, Damoiseaux R, Scumpia PO, Smale ST, Williams KJ, Tontonoz P, and Bensinger SJ

Subjects
Animals, Bacteria immunology, Bacteria metabolism, Bacterial Proteins administration & dosage, Bacterial Proteins immunology, Bacterial Proteins metabolism, Bacterial Toxins metabolism, Cell Membrane metabolism, Cell Membrane Permeability immunology, Cells, Cultured, Disease Models, Animal, Disease Susceptibility immunology, Female, Host Microbial Interactions immunology, Humans, Intravital Microscopy, Male, Mice, Mice, Transgenic, Phagocytes cytology, Phagocytes metabolism, Primary Cell Culture, Steroid Hydroxylases genetics, Steroid Hydroxylases metabolism, Streptolysins administration & dosage, Streptolysins metabolism, Bacterial Infections immunology, Bacterial Toxins immunology, Hydroxycholesterols metabolism, Interferons isolation & purification, Phagocytes immunology, Streptolysins immunology
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.

Published
2020
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2. Interferon-mediated reprogramming of membrane cholesterol to evade bacterial toxins

Author

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

Subjects
Male, Cell Membrane Permeability, Intravital Microscopy, Cells, Bacterial Toxins, Primary Cell Culture, Immunology, Transgenic, Vaccine Related, Mice, Bacterial Proteins, Biodefense, 2.1 Biological and endogenous factors, Animals, Humans, Aetiology, Phagocytes, Cultured, Bacteria, Host Microbial Interactions, Animal, Prevention, Cell Membrane, Bacterial Infections, Hydroxycholesterols, Infectious Diseases, Disease Models, Steroid Hydroxylases, Streptolysins, lipids (amino acids, peptides, and proteins), Female, Disease Susceptibility, Interferons, Infection
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.

Published
2020

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