Letter abstract
Nature Medicine 14, 949 - 953 (2008)
Published online: 10 August 2008 | doi:10.1038/nm.1855
Catapult-like release of mitochondrial DNA by eosinophils contributes to antibacterial defense
Shida Yousefi1, Jeffrey A Gold2, Nicola Andina1, James J Lee3, Ann M Kelly2, Evelyne Kozlowski1, Inès Schmid1, Alex Straumann4, Janine Reichenbach5, Gerald J Gleich6 & Hans-Uwe Simon1
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-
–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.
- Institute of Pharmacology, University of Bern, Friedbühlstrasse 49, CH-3010 Bern, Switzerland.
- Division of Pulmonary and Critical Care, Oregon Health and Sciences University, 3181 Southwest Sam Jackson Park Road, Portland, Oregon 97239, USA.
- Department of Biochemistry and Molecular Biology, Mayo Clinic Arizona, 13400 East Shea Boulevard, Scottsdale, Arizona 85259, USA.
- Department of Gastroenterology, Kantonsspital Olten, Römerstrasse 7, CH-4600 Olten, Switzerland.
- University Children's Hospital, Steinwiesstrasse 75, CH-8032 Zurich, Switzerland.
- Department of Dermatology, University of Utah, 30 North 1900 East, Salt Lake City, Utah 84132-2409, USA.
Correspondence to: Shida Yousefi1 e-mail: shida.yousefi@pki.unibe.ch
Correspondence to: Hans-Uwe Simon1 e-mail: hus@pki.unibe.ch
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