Neutrophils and aquatic pathogens

Neutrophilic granulocytes are short-lived cells continuously circulating in the vascular system of vertebrates. They play a basic and decisive role in the innate immune defence of the hosts against all types of pathogenic microorganisms.

Based on a literature study, the functions of neutrophils and cells with similar functions are described. The study places special emphasis on organisms in the aquatic environment and the pathogens occurring in that particular environment.

The evolutionary origin of this specific cell type is not clear, but its most basic traits (recognition of foreign elements, extracellular trap release, phagocytosis and elimination of ingested material) are found in phagocytes in members of evolutionary ancient invertebrate groups spanning from amoebae, sponges, sea-anemones, mollusks (snails and mussels), arthropods (crustaceans and insects) to echinoderms (sea stars and sea urchins). Their functions as innate immune sentinels and effector cells in these groups are well described. Neutrophilic granulocytes with elongated and lobed nuclei (possibly allowing cell movements through narrow extracellular spaces and leaving space for phagosomes) occur in vertebrates including fish, amphibians, reptiles, birds and mammals although the morphology of the nucleus, stainability of cytoplasmic granula, and the antimicrobial armament vary among groups. Following the pathogen invasion of a fish host, the neutrophils migrates from the vascular system into the infection focus. They apply their PRRs (including TLRs) to recognize the invader as non-self, produce netosis by casting extracellular chromatin containing traps in the microenvironment. These nets assist the immobilization of invading microbes and prevents their further spread. The cells attach to and engulf the microbes by phagocytosis, whereafter they eliminate the pathogen in phagolysosomes equipped with a range of killing mechanisms and attract, by release of chemokines, additional immune cells (monocytes, macrophages and lymphocytes) to the site of invasion. Their role in innate immunity of fish hosts towards aquatic pathogens has been elucidated by in vivo and in vitro studies. Neutrophils interact with virus (e.g. IPNV and VHSV), bacteria (e.g. Aeromonas, Vibrio, Edwardsiella, Mycobacterium and Renibacterium) and parasites, including monogeneans (Gyrodactylus), cestodes (Diphyllobothrium), trematodes (Diplostomum) and ciliates (Ichthyophthirius and Philasterides). Despite the decisive function of neutrophils in innate immunity and early protection, the excessive production of ROS, RNS and NETs may lead to pathological disturbances in the host, which are exacerbated if the pathogens evolve immune evasion mechanisms.

Neutrophils in aquatic organisms play a central role in innate immunity but may serve as a toll and a support in acquired protection. The strong impact of the cellular reactions not only on pathogen but also on host tissues emphasizes that an optimal immune reaction is balanced, involves targeted and specific effector mechanisms, which leaves a minimum of collateral damage in host organs.