Abstract
Macrophages are found across all vertebrate species, reside in virtually all animal tissues, and play critical roles in host protection and homeostasis. Various mechanisms determine and regulate the highly plastic functional phenotypes of macrophages, including antimicrobial host defenses (pro-inflammatory, M1-type), and resolution and repair functions (anti-inflammatory/regulatory, M2-type). The study of inflammatory macrophages in immune defense of teleosts has garnered much attention, and antimicrobial mechanisms of these cells have been extensively studied in various fish models. Intriguingly, both similarities and differences have been documented for the regulation of lower vertebrate macrophage antimicrobial defenses, as compared to what has been described in mammals. Advances in our understanding of the teleost macrophage M2 phenotypes likewise suggest functional conservation through similar and distinct regulatory strategies, compared to their mammalian counterparts. In this review, we discuss the current understanding of the molecular mechanisms governing teleost macrophage functional heterogeneity, including monopoetic development, classical macrophage inflammatory and antimicrobial responses as well as alternative macrophage polarization towards tissues repair and resolution of inflammation.
Highlights
Macrophage lineage cells present a remarkably versatile array of functional specializations across vertebrates
Much of our understanding of macrophage biology comes from research in mammalian models, where distinct macrophage subsets of have been characterized, including classically activated cells by interferons (IFN) and tumor necrosis factor alpha (TNFα) (M1); alternatively activated cells by IL-4 and IL-13 (M2a); macrophages activated by immune complexes or apoptotic cells (M2b); and regulatory macrophages, deactivated by IL-10, TGF-β, or glucocorticoids (M2c), which culminate in the various effector subtypes, broadly described as having a “kill” or “heal” response
Akin to their mammalian counterparts, macrophages of teleost fish exhibit a plethora of functional roles including those pertaining to homeostasis, as well as host immune defenses, and are largely governed by their respective tissue niches and microenvironments
Summary
Macrophage lineage cells present a remarkably versatile array of functional specializations across vertebrates. The best characterized macrophage phenotype is that comparable to the M1 activation state, which serves a critical role in host protection. These cells may rapidly kill pathogens by engulfment and production of toxic reactive intermediates [3], phagolysosomal acidification [4], and restriction of nutrient availability [5]. Efforts to characterize alternative activation states of teleost macrophages are focusing on the biology of fish IL4 and IL13 homologues (IL4/13A and IL4/13B). Similar deactivating roles of glucocorticoids (GC), immune complexes, IL-10, and TGF-β have been demonstrated in teleosts, suggesting conserved functions of these ligands in deactivating or aiding in the tissue repair [8,9,10]. This review discusses bony fish macrophage development, polarization, and functional responses, comprehensively coalescing the current understanding of teleost macrophage biology
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