Neutrophil Development, Migration, and Function in Teleost Fish

Abstract

It is now widely recognized that neutrophils are sophisticated cells that are critical to host defense and the maintenance of homeostasis. In addition, concepts such as neutrophil plasticity are helping to define the range of phenotypic profiles available to cells in this group and the physiological conditions that contribute to their differentiation. Herein, we discuss key features of the life of a teleost neutrophil including their development, migration to an inflammatory site, and contributions to pathogen killing and the control of acute inflammation. The potent anti-microbial mechanisms elicited by these cells in bony fish are a testament to their long-standing evolutionary contributions in host defense. In addition, recent insights into their active roles in the control of inflammation prior to induction of apoptosis highlight their importance to the maintenance of host integrity in these early vertebrates. Overall, our goal is to summarize recent progress in our understanding of this cell type in teleost fish, and to provide evolutionary context for the contributions of this hematopoietic lineage in host defense and an efficient return to homeostasis following injury or infection.

Keywords: comparative immunology; inflammation; inflammatory resolution; innate immunity; neutrophils; teleost fish.

Figure 1

Contributions of neutrophils to the induction, regulation, and resolution of the acute inflammatory response in teleost fish. Peritoneal injection of zymosan results in the release of proinflammatory cytokines, such as CXCL8, TNF-α, IL-1β, and IFN-γ, and chemoattractants like CXCL8 and LTB₄, inducing the infiltration of neutrophils and other leukocytes. Inflammatory neutrophils enter the site of inflammation and are subsequently activated by the inflammatory milieu, resulting in increased ROS production and the release of more LTB₄ (pro-inflammatory lipid mediator). As inflammation progresses, a transition from pro-inflammatory to pro-resolution begins to occur (18–24 hpi). Neutrophils then alter their production of lipid mediators to increase the release of LXA₄, followed by an entry into apoptotic cascades, peaking at 24 hpi. We hypothesize that this switch from LTB4 to LXA4 is mediated, at least in part, by the release of PGE₂ from local cells (grayed out in model with question marks). The local inflammatory milieu slowly becomes pro-resolving as macrophages are stimulated by LXA₄, decreasing their production of ROS and increasing their uptake of apoptotic neutrophils. This progression eventually leads to the return to homeostasis by 72 hpi. The relationship between neutrophil production within the kidney hematopoietic tissue, their migration through the blood, and infiltration into the challenge site highlight unique features of the teleost system.