Abstract

Leukocytes play a major role in combating infections either by phagocytosis, release of antimicrobial granules, or extracellular trap (ET) formation. ET formation is preceded by a certain leukocyte cell death form, known as ETosis, an evolutionarily conserved mechanism of the innate immune system also observed in marine mammals. Besides several biomolecules and microbial stimuli, marine mammal ETosis is also trigged by various terrestrial protozoa and metazoa, considered nowadays as neozoan parasites, which are circulating in oceans worldwide and causing critical emerging marine diseases. Recent studies demonstrated that pinniped- and cetacean-derived polymorphonuclear neutrophils (PMNs) and monocytes are able to form different phenotypes of ET structures composed of nuclear DNA, histones, and cytoplasmic peptides/proteases against terrestrial apicomplexan parasites, e.g., Toxoplasma gondii and Neospora caninum. Detailed molecular analyses and functional studies proved that marine mammal PMNs and monocytes cast ETs in a similar way as terrestrial mammals, entrapping and immobilizing T. gondii and N. caninum tachyzoites. Pinniped- and cetacean leukocytes induce vital and suicidal ETosis, with highly reliant actions of nicotinamide adenine dinucleotide phosphate oxidase (NOX), generation of reactive oxygen species (ROS), and combined mechanisms of myeloperoxidase (MPO), neutrophil elastase (NE), and DNA citrullination via peptidylarginine deiminase IV (PAD4).This scoping review intends to summarize the knowledge on emerging protozoans in the marine environment and secondly to review limited data about ETosis mechanisms in marine mammalian species.

Highlights

  • Innate immune responses are important mechanisms of the host defense against infections, either protecting non-vertebrate organisms or synergizing adaptive immunity in vertebrate animals [1,2]

  • Marine mammals are highly valuable with respect to comparative and evolutionary immunology since they are the only descendants of primitive terrestrial mammals which returned to the sea and their immune system was initially adapted to a terrestrial existence, including host–parasite interactions that have been re-evolved in aquatic ecosystems [15]

  • Further studies are required concerning the different molecular activation mechanisms involved in ETosis, those ones associated with the leukocyte type involved in this process, and the intraspecific differences between the diverse pathogenic agents and even between the marine mammals should be considered

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Summary

Introduction

Innate immune responses are important mechanisms of the host defense against infections, either protecting non-vertebrate organisms or synergizing adaptive immunity in vertebrate animals [1,2] These responses are performed by anatomical and physiological barriers (e.g., mucociliary blanket), antimicrobial factors (e.g., complement, lysozyme, lactoferrin, defensins and reactive oxygen and nitrogen intermediates), and by professional mononuclear phagocytes (e.g., polymorphonuclear neutrophils (PMNs), monocytes, macrophages), all of them representing the first line of defense against a vast number of potentially pathogenic agents [3]. These leukocytes are able to entrap, phagocytize, and damage invasive microorganisms, but at the same time they release. It reviews the innate effector defense mechanism of ETosis and summarizes very limited data on T. gondii- and Neospora caninum-induced ETosis in pinnipeds and cetaceans, thereby highlighting the relevance of this ancient, conserved and effective defense mechanism against these parasites currently circulating in marine environments [31,32,33,34,35,36,37]

Marine Environment Affected by Emerging Neozoan Parasites
ETosis in Terrestrial and Marine Mammals
Conclusions
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