Article abstract
Nature Genetics 39, 1453 - 1460 (2007)
Published online: 18 November 2007 | doi:10.1038/ng.2007.25
ATP-sensitive potassium channels mediate survival during infection in mammals and insects
Ben Croker1,4, Karine Crozat1, Michael Berger1, Yu Xia1, Sosathya Sovath1, Lana Schaffer2, Ioannis Eleftherianos3, Jean-Luc Imler3 & Bruce Beutler1
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 
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 (KATP) 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, KATP 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.
- Department of Genetics, IMM-31, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
- DNA Array Core Facility, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
- UPR 9022 – CNRS, Institut de Biologie Moléculaire et Cellulaire, 15 rue René Descartes, 67084 Strasbourg cedex, France.
- Present Address: Cancer and Haematology Division, The Walter and Eliza Hall Institute, 1G Royal Parade, Parkville, Victoria 3050, Australia.
Correspondence to: Bruce Beutler1 e-mail: bruce@scripps.edu
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
RESEARCH
Identification of Lps2 as a key transducer of MyD88-independent TIR signallingNature Article (14 Aug 2003)
See all 2 matches for Research
