title: Catapult-like release of mitochondrial DNA by eosinophils contributes to antibacterial defense.
abstract: Although eosinophils are considered useful in defense mechanisms against parasites, their exact function in innate immunity remains unclear. The aim of this study is to better understand the role of eosinophils within the gastrointestinal immune system. We show here that lipopolysaccharide from Gram-negative bacteria activates interleukin-5 (IL-5)- or interferon-gamma-primed eosinophils to release mitochondrial DNA in a reactive oxygen species-dependent manner, but independent of eosinophil death. Notably, the process of DNA release occurs rapidly in a catapult-like manner--in less than one second. In the extracellular space, the mitochondrial DNA and the granule proteins form extracellular structures able to bind and kill bacteria both in vitro and under inflammatory conditions in vivo. Moreover, after cecal ligation and puncture, Il5-transgenic but not wild-type mice show intestinal eosinophil infiltration and extracellular DNA deposition in association with protection against microbial sepsis. These data suggest a previously undescribed mechanism of eosinophil-mediated innate immune responses that might be crucial for maintaining the intestinal barrier function after inflammation-associated epithelial cell damage, preventing the host from uncontrolled invasion of bacteria.
authors.affiliation: Institute of Pharmacology, University of Bern, Friedbühlstrasse 49, CH-3010 Bern, Switzerland. shida.yousefi@pki.unibe.ch
authors.forename: Shida
authors.initials: S
authors.lastname: Yousefi
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Gold
authors.forename: Nicola
authors.initials: N
authors.lastname: Andina
authors.forename: James J
authors.initials: JJ
authors.lastname: Lee
authors.forename: Ann M
authors.initials: AM
authors.lastname: Kelly
authors.forename: Evelyne
authors.initials: E
authors.lastname: Kozlowski
authors.forename: Inès
authors.initials: I
authors.lastname: Schmid
authors.forename: Alex
authors.initials: A
authors.lastname: Straumann
authors.forename: Janine
authors.initials: J
authors.lastname: Reichenbach
authors.forename: Gerald J
authors.initials: GJ
authors.lastname: Gleich
authors.forename: Hans-Uwe
authors.initials: HU
authors.lastname: Simon
mesh_terms: D000818:Animals; D001419:Bacteria / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D004272:DNA, Mitochondrial / Q000235:genetics*; D004804:Eosinophils / Q000737:chemistry / Q000276:immunology* / Q000502:physiology; D005767:Gastrointestinal Diseases / Q000276:immunology*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015848:Interleukin-5 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D017382:Reactive Oxygen Species / Q000378:metabolism; D018805:Sepsis / Q000276:immunology*
chemical_list: D004272:DNA, Mitochondrial; D015848:Interleukin-5; D017382:Reactive Oxygen Species