Extracellular Traps: An Ancient Weapon of Multiple Kingdoms

Abstract

The discovery, in 2004, of extracellular traps released by neutrophils has extended our understanding of the mode of action of various innate immune cells. This fascinating discovery demonstrated the extracellular trapping and killing of various pathogens by neutrophils. During the last decade, evidence has accumulated showing that extracellular traps play a crucial role in the defence mechanisms of various cell types present in vertebrates, invertebrates, and plants. The aim of this review is to summarise the relevant literature on the evolutionary history of extracellular traps used as a weapon in various kingdoms of life. Biology 2020, 9, 34 2 of 23On the basis of findings from several studies mostly performed with human and murine neutrophils, the following three different pathways that lead to the formation of ETs by innate immune cells have been identified: (1) Release of nuclear DNA by ETosis, a suicidal cell death associated with the rupture of the nuclear membrane prior to cell lysis [14,15]; (2) vesicular release of nuclear DNA by viable cells [16,17]; and (3) release of mitochondrial DNA [18,19]. However, the exact molecular mechanisms leading to one or the other phenotype of ET formation has still not been entirely clarified. A group of renowned scientists and experts on NETs has recently published an opinionated review on the subject due to the abundance of available data that has also led to some confusion in the NET/ET research community because of contradictory results and divergent scientific concepts, for example, the molecular pathways of ET formation or the origin of the DNA that forms the ET scaffold [20]. There is a strong consensus about the composition of ETs among the findings that NETs contain a high amount of granule proteins, for example, cell-type-specific proteases and other antibacterial molecules that are associated with DNA-histone complexes. However, it is still unclear how different triggers or pathways have led to phenotypical differences about the source of DNA or viability of the ET-releasing cell.Comparison of ET phenotypical differences between host species in relation to evolutionary aspects, especially by comparing data from phylogenetic groups, would help to understand the pathways of ET formation in more detail.

What Is the Evolutionary Fingerprint in Neutrophil Granulocytes?

“…This statement emphasized a common basis of activity: the microbicidal and phagocytic aspects of neutrophil actions [87]. Other conserved antimicrobial reactions comprise degranulation and NET-formation [9].…”

“…Still, there are no reports about extracellular traps in amphibians and reptiles, only hints about heterophil projections in a turtle [168]. Apart from this common ground of building extracellular traps, originating from neutrophils or other cells, similarities have also been described in the composition of these traps, as well as in the provoking stimuli [9]. Nevertheless, if little or no granule protein is present in a species, the NETs structures may differ with respect to the embedded proteins.…”

“…Thereby, the web-like formations catch and combat pathogens, but also detrimental effects such as a contribution to certain autoimmune diseases may occur [ 166 , 167 ]. The conservation of this mechanism among species has recently been highlighted in a review by Neumann et al [ 9 ]. Its occurrence is reported in various vertebrate species: mammals, including marsupials, birds, and fish.…”

“…A widely known example would be the occurrence of heterophils instead of neutrophils in birds, as well as in some mammalian and reptile species. Furthermore, besides morphologic differences, species variations in neutrophil function exist, as it has been recently summarized in the regard of NETs [9].…”

Conservation of Cell Communication Systems in Invertebrate Host–Defence Mechanisms: Possible Role in Immunity and Disease

“…In a broader light, ETs can represent a noncanonical intercellular communication in immune response [ 7 ]. During the last decade, evidence has accumulated showing that ETs play a crucial role in the defence mechanisms of various cell types, not only in mammals, but also in other vertebrates, as well as in invertebrates and plants, suggesting that ETs are one of the primordial and evolutionary ancient mechanism of host defence [ 12 ]. Many studies are available in marine invertebrates, where ETs have been first described in crustacean haemocytes.…”