Invertebrate extracellular phagocyte traps show that chromatin is an ancient defence weapon

Abstract

Controlled release of chromatin from the nuclei of inflammatory cells is a process that entraps and kills microorganisms in the extracellular environment. Now termed ETosis, it is important for innate immunity in vertebrates. Paradoxically, however, in mammals, it can also contribute to certain pathologies. Here we show that ETosis occurs in several invertebrate species, including, remarkably, an acoelomate. Our findings reveal that the phenomenon is primordial and predates the evolution of the coelom. In invertebrates, the released chromatin participates in defence not only by ensnaring microorganisms and externalizing antibacterial histones together with other haemocyte-derived defence factors, but crucially, also provides the scaffold on which intact haemocytes assemble during encapsulation; a response that sequesters and kills potential pathogens infecting the body cavity. This insight into the early origin of ETosis identifies it as a very ancient process that helps explain some of its detrimental effects in mammals.

Antimicrobial proteins: From old proteins, new tricks

“…An equivalent process has subsequently been reported for chicken heterophils (Chuammitri et al, 2009) and fish phagocytes (Palić et al, 2007;Brogden et al, 2014). The process is not confined to vertebrates, as similar entrapment of bacteria on externalized chromatin has been demonstrated with haemocytes from crab, C. maenas (Robb et al, 2014) (Fig. 1) and shrimp, L. vannamei.…”

The paralytic shellfish toxin, saxitoxin, enters the cytoplasm and induces apoptosis of oyster immune cells through a caspase-dependent pathway

“…2009) and ETosis (Robb et al 2014). The production of ROS in STX-treated hemocytes was therefore measured over the course of 2 h and compared to ROS production in hemocytes exposed to zymosan, a reagent that induces a strong oxidative burst in oyster hemocytes (Poirier et al 2014).…”

“…Thus, apoptosis plays an important role in mollusc immunity (Sokolova 2009) and, more generally, in invertebrate immunity (Sokolova 2009;Terahara and Takahashi 2008;Hughes et al 2010;Zhang et al 2011). Hemocytes from bivalve molluscs also respond to infection and damage through additional cell death processes such as ETosis, which leads to the extracellular release of antimicrobial DNA traps (Poirier et al 2014;Robb et al 2014).…”

NETs in pneumonia: is just enough the right amount?

“…Since the first description of NETs in 2004 their role as a potent mechanism to deal with invading pathogens has been suggested [4], and the fact that this process is highly conserved in the animal [5] and plant kingdom [6] has served to underline this. However, the overall contribution of NETs to bacterial killing in humans, in vivo, remains unclear, particularly in comparison to other processes such as phagocytosis.…”