Ctenophore extracellular DNA traps demonstrate conserved antimicrobial behaviors present at the emergence of animals

Abstract

The formation of extracellular DNA traps (ETosis) is a first response mechanism by specific immune cells following exposure to microbes ^1,2. First characterized in vertebrate neutrophils, cells capable of ETosis have been recently discovered in several invertebrate taxa and the formation of invertebrate DNA traps has been most thoroughly examined in bivalves ^3-5. Here we report that ctenophores – thought to have diverged very early from the metazoan stem lineage ^6,7 – possess immune cell types capable of ETosis, suggesting that this cellular immune response behavior was likely present early in metazoan evolution. To assess conservation of ET activation between evolutionarily distant phyla, we deployed a comparative approach integrating data from the model ctenophore Mnemiopsis leidyi and the oyster Crassostrea gigas to develop a novel imaging analysis pipeline to quantify ETosis in large numbers of cells. We demonstrate that both Mnemiopsis and Crassostrea immune cells can undergo ETosis after exposure to diverse microbes and pharmacological stimuli. Our results suggest that the range of cellular immune behaviors and signaling cascades that produce extracellular DNA traps were likely present prior to the divergence of extant metazoan lineages and thus ETosis represents an evolutionarily ancient defense against pathogens existing at the dawn of animal multicellularity.