Microfilariae Trigger Eosinophil Extracellular DNA Traps in a Dectin-1-Dependent Manner

Abstract

Eosinophils mediate protection against filarial nematodes. Our results demonstrate that eosinophil extracellular traps (EETosis) are induced by microfilariae and infective L3 larvae of Litomosoides sigmodontis. These extracellular DNA traps inhibit microfilariae motility in a DNA- and contact-dependent manner in vitro. Accordingly, microfilariae-injection triggers DNA release in an eosinophil-dependent manner in vivo and microfilariae covered with DNA traps are cleared more rapidly. Using dectin-1, we identify the required receptor for the microfilariae-induced EETosis, whereas signaling via other C-type lectin receptors, prior priming of eosinophils, and presence of antibodies are not required. The DNA released upon microfilariae-induced EETosis is mainly of mitochondrial origin, but acetylated and citrullinated histones are found within the traps. We further demonstrate that the presented DNA-dependent inhibition of microfilariae motility by eosinophils represents a conserved mechanism, as microfilariae from L. sigmodontis and the canine heartworm Dirofilaria immitis induce ETosis in murine and human eosinophils.

Keywords: Dirofilaria immitis; ETosis; L3 larva; Litomosoides sigmodontis; dectin-1; eosinophils; extracellular DNA traps; filaria; microfilaria; protective immunity.