L’Inflammation chez la Drosophile

@article{eleftherianos_atp-sensitive_2011,

title = {ATP-sensitive potassium channel (K(ATP))-dependent regulation of cardiotropic viral infections},

author = {Ioannis Eleftherianos and Sungyong Won and Stanislava Chtarbanova and Barbara Squiban and Karen Ocorr and Rolf Bodmer and Bruce Beutler and Jules A Hoffmann and Jean-Luc Imler},

doi = {10.1073/pnas.1108926108},

issn = {1091-6490},

year  = {2011},

date = {2011-07-01},

journal = {Proceedings of the National Academy of Sciences of the United States of America},

volume = {108},

number = {29},

pages = {12024--12029},

abstract = {The effects of the cellular environment on innate immunity remain poorly characterized. Here, we show that in Drosophila ATP-sensitive potassium channels (K(ATP)) mediate resistance to a cardiotropic RNA virus, Flock House virus (FHV). FHV viral load in the heart rapidly increases in K(ATP) mutant flies, leading to increased viremia and accelerated death. The effect of K(ATP) channels is dependent on the RNA interference genes Dcr-2, AGO2, and r2d2, indicating that an activity associated with this potassium channel participates in this antiviral pathway in Drosophila. Flies treated with the K(ATP) agonist drug pinacidil are protected against FHV infection, thus demonstrating the importance of this regulation of innate immunity by the cellular environment in the heart. In mice, the Coxsackievirus B3 replicates to higher titers in the hearts of mayday mutant animals, which are deficient in the Kir6.1 subunit of K(ATP) channels, than in controls. Together, our data suggest that K(ATP) channel deregulation can have a critical impact on innate antiviral immunity in the heart.},

keywords = {Animals, Heart, HeLa Cells, hoffmann, Humans, imler, Immunity, Immunoblotting, Inbred C57BL, Innate, KATP Channels, M3i, Mice, Nodaviridae, Pinacidil, Reverse Transcriptase Polymerase Chain Reaction, RNA Interference, Tolbutamide, Viral Load, Viremia},

pubstate = {published},

tppubtype = {article}

}

@article{croker_atp-sensitive_2007,

title = {ATP-sensitive potassium channels mediate survival during infection in mammals and insects},

author = {Ben Croker and Karine Crozat and Michael Berger and Yu Xia and Sosathya Sovath and Lana Schaffer and Ioannis Eleftherianos and Jean-Luc Imler and Bruce Beutler},

doi = {10.1038/ng.2007.25},

issn = {1546-1718},

year  = {2007},

date = {2007-01-01},

journal = {Nature Genetics},

volume = {39},

number = {12},

pages = {1453--1460},

abstract = {Specific homeostatic mechanisms confer stability in innate immune responses, preventing injury or death from infection. Here we identify, from a screen of N-ethyl-N-nitrosourea-mutagenized mice, a mutation causing both profound susceptibility to infection by mouse cytomegalovirus and approximately 20,000-fold sensitization to lipopolysaccharide (LPS), poly(I.C) and immunostimulatory (CpG) DNA. The LPS hypersensitivity phenotype is not suppressed by mutations in Myd88, Trif, Tnf, Tnfrsf1a, Ifnb, Ifng or Stat1, genes contributing to LPS responses, and results from an abnormality extrinsic to hematopoietic cells. The phenotype is due to a null allele of Kcnj8, encoding Kir6.1, a protein that combines with SUR2 to form an ATP-sensitive potassium channel (K(ATP)) expressed in coronary artery smooth muscle and endothelial cells. In Drosophila melanogaster, suppression of dSUR by RNA interference similarly causes hypersensitivity to infection by flock house virus. Thus, K(ATP) evolved to serve a homeostatic function during infection, and in mammals it prevents coronary artery vasoconstriction induced by cytokines dependent on TLR and/or MDA5 immunoreceptors.},

keywords = {Animals, ATP-Binding Cassette Transporters, Cloning, Coronary Vessels, Crosses, Ethylnitrosourea, Genetic, Homozygote, imler, infection, Inwardly Rectifying, KATP Channels, Lipopolysaccharides, M3i, Mice, Molecular, Mutagenesis, Potassium Channels, Sulfonylurea Receptors},

pubstate = {published},

tppubtype = {article}

}