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

Yousefi, S. and Gold, J. A. and Andina, N. and Lee, J. J. and Kelly, A. M. and Kozlowski, E. and Schmid, I. and Straumann, A. and Reichenbach, J. and Gleich, G. J. and Simon, H. U.. (2008) Catapult-like release of mitochondrial DNA by eosinophils contributes to antibacterial defense. Nature medicine, Vol. 14, H. 9. pp. 949-953.

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Official URL: http://edoc.unibas.ch/dok/A6003867

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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.
Faculties and Departments:03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Gastroenterologie
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Gastroenterologie
UniBasel Contributors:Straumann, Alex
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Nature Publishing
ISSN:1078-8956
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:21 Jun 2013 12:29
Deposited On:21 Jun 2013 12:23

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