ATP-sensitive potassium channels mediate survival during infection in mammals and insects

Ben Croker, Karine Crozat, Michael Berger, Yu Xia, Sosathya Sovath, Lana Schaffer, Ioannis Eleftherianos, Jean Luc Imler, Bruce Beutler

Research output: Contribution to journalArticle

43 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1453-1460
Number of pages8
JournalNature genetics
Volume39
Issue number12
DOIs
StatePublished - Dec 1 2007

ASJC Scopus subject areas

  • Genetics

Fingerprint Dive into the research topics of 'ATP-sensitive potassium channels mediate survival during infection in mammals and insects'. Together they form a unique fingerprint.

Cite this