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

Yousefi, S. et al. Nat. Med. 949–953 (2008).

Speaker: Tsung-Ying Hsieh (謝宗穎)             Time: 14:00~15:00, Dec. 24, 2008

Commentator: Dr. Yee-Shin Lin (林以行老師)     Place: Room 601

Abstract:

The eosinophils are multifunctional leukocytes involved in numerous inflammatory processes including parasite infection, allergic diseases and other inflammatory response. It was reported that many eosinophils reside within the lamina propria of gastrointestinal tract and they will increase in many intestinal disorders including eosinophil-associated gastrointestinal diseases (EGIDs) and inflammatory bowel diseases (IBDs). After IL-5 stimulation, eosinophils can be attracted by eotaxins to inflammatory site. After reaching inflammatory site, they secretcytotoxic granule proteins which are capable of destroying pathogen and contrary function inducing tissue damage including major basic protein (MBP) and eosinophil cationic protein (ECP) . In previous studies, it has been found that stimulated neutrophils can produce an extracellular structure called neutrophil extracellular trap (NET) that captures and kills microorganisms. However, the exact role of eosinophils in mediating innate immunity remains obscure. In this paper, the authors found a new mechanism of eosinophils to defend bacterial infection. First, they found that extracellular DNA was stained with PI on ECP-positive cells in the intestine of IBD patients. In in vitro experiments, the IL-5 or IFNg-primed eosinophils would release DNA and granular proteins after being stimulated with eotaxin, C5a or LPS. The authors also found that the DNA release was ROS dependent. It could be blocked with an NADPH oxidase inhibitor (DPI). Next, they showed that released DNA was mitocondrial DNA rather than nuclear DNA. When cocultured with E.coli, the eosinophil performed cell-mediated bactericidal activity which could be blocked with DNase but not with cytochalasin D, a phagocytosis inhibitor. Moreover, in an animal model of sepsis using cecal ligation and puncture (CLP), the Il-5 transgenic mice but not wild type animals showed intestinal eosinophil infiltration and extracellular DNA deposition which appeared to be protective for the mice. The authors suggested that eosinophils play a unique role in defense on epithelial barriers and use a novel mechanism to contribute to host defense in innate immunity.

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