Catapult-like release of mitochondrial DNA by eosinophils contributes to antibacterial defense

Yousefi, Shida; Gold, Jeffrey A; Andina, Nicola; Lee, James J; Kelly, Ann M; Kozlowski, Evelyne; Schmid, Inès; Straumann, Alex; Reichenbach, Janine; Gleich, Gerald J; Simon, Hans-Uwe (2008). Catapult-like release of mitochondrial DNA by eosinophils contributes to antibacterial defense. Nature medicine, 14(9), pp. 949-53. New York, N.Y.: Nature Publishing Group 10.1038/nm.1855

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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.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology
UniBE Contributor:	Yousefi, Shida, Simon, Hans-Uwe
ISSN:	1078-8956
ISBN:	18690244
Publisher:	Nature Publishing Group
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 15:03
Last Modified:	05 Dec 2022 14:19
Publisher DOI:	10.1038/nm.1855
PubMed ID:	18690244
Web of Science ID:	000258988600027
URI:	https://boris.unibe.ch/id/eprint/27545 (FactScience: 108783)