Editorial: Cell-mediated innate immunity in aquatic invertebrates and fish: what’s new?

key words: innate immune cells; aquatic environment; host-pathogen interaction; aquaculture health management; novel cell functions; pathogen sensing; evolution of innate immunity.The study of defense strategies and innate immune mechanisms in marine organisms-spanning invertebrates and vertebrates-continues to reveal remarkable complexity shaped by diverse biotic and abiotic pressures in aquatic environments. Far from being a simple first line of defense, innate immunity in these organisms exhibit sophisticated cellular and molecular processes that rival those of higher vertebrates. As highlighted in this Reseach Topic, the innate immune response-including cell-mediated processes-is central to rapid and effective protection against a broad spectrum of invaders. Recent findings reveal unexpected immunological diversity and functional parallels between immune cells of invertebrates, fish, and mammals, identifying conserved chemotactic, phagocytic, and inflammatory pathways. Despite these advances, significant gaps remain in understanding the mechanistic basis of cell-mediated immunity in invertebrates and teleosts. Although these taxa possess broad immune gene repertoires, their functional roles are only partially characterized.Delisle and colleagues report a major advance in oyster immunology by demonstrating that inactivated Ostreid herpesvirus-1 (OsHV-1) can trigger an innate immune response in Pacific oyster hemocytes. Using an innovative in vitro assay with Crassostrea gigas hemocytes from juveniles susceptible to OsHV-1, authors tested multiple antigen preparations, including chemically/physically inactivated OsHV-1, viral DNA, and protein extracts. Ten different antigen preparations successfully stimulated hemocyte immune activity, without cytotoxic effects, benchmarked against the standard immune stimulant Poly (I:C). These findings represent a significant step toward developing of pseudo-vaccines for oysters, offering promising strategies for managing polymicrobial diseases in aquaculture, such as Pacific oyster mortality syndrome (POMS), which has severely impacted global Pacific oyster aquaculture.Emerging research on echinoderms reveals an astonishing immune complexity, reshaping the understanding of their immune cells and the molecular mechanisms driving their defense strategies. A striking example comes from the sea cucumber Holothuria forskali. In their study, Noé and colleagues overturned the long-standing belief that reddish coelomocytes were hemoglobincontaining respiratory cells. Through integrative morphological and multi-omic analyses, authors demonstrate that these cells accumulate high levels of carotenoids, potent antioxidant compounds that confer their pigmentation. Based on these findings, the cells were redefined as "carotenocytes," reflecting their role as specialized immune effectors that form antioxidant shells around pathogenencapsulating aggregates to mitigate oxidative stress. This discovery represents a paradigm shift in understanding coelomocyte function and highlights the evolutionary sophistication of echinoderm immunity.The California purple sea urchin Strongylocentrotus purpuratus provides another compelling example of sophisticated innate immunity. The defense of sea urchins is driven by the high variability of its SpTransformer (SpTrf) protein family, where different isoforms exhibit distinct capabilities in binding pathogens and augmenting phagocytosis. In a recent study, Crow and colleagues explored the role of six recombinant SpTrf proteins as opsonins in S. purpuratus. Their work demonstrates isoform-specific roles in opsonization and phagocytosis, with recombinant SpTrf proteins enhancing immune activity in distinct phagocyte subtypes. When exposed to beads coated with different rSpTrf isoforms, polygonal phagocytes exhibit selective binding and phagocytosis for a subset of rSpTrf::beads, discoidal cells maintain baseline phagocytosis for all rSpTrf::beads, and small coelomocytes, previously inferred to have immune roles, are confirmed as phagocytes through their ability to engulf rSpTrf::beads. These findings underscore a functional specialization, creating a complex and effective invertebrate system for neutralizing a wide range of pathogens.To understand how functional specialization has evolved in a different evolutionary lineage possessing both innate and adaptive immunity, we now turn our focus to fish. Contrary to the conventional view of red blood cells (RBCs) as oxygen carriers, research on teleost fish reveals them to be actively involved in the immune response. Unlike anucleate mammalian erythrocytes, fish RBCs retain their nucleus, enabling transcription and protein synthesis essential for immune functions. A study by Majstokovic and colleagues on the common carp Cyprinus carpio provides compelling evidence for the multifaceted immune role of RBCs. Using both in vitro exposure to Aeromonas hydrophila and in vivo infections, authors demonstrate that RBCs express pattern recognition receptors, including Toll-like receptors (TLRs), enabling pathogen detection, secrete proinflammatory cytokines, produce reactive oxygen species, and exhibit phagocytic activity. These findings position fish RBCs as immune sentinels, advancing our understanding of conserved immune mechanisms and their evolutionary significance in teleosts. Such insights have remarkable implications for aquaculture health management and the development of novel immunostimulatory strategies.Complementing these findings, Dezfuli and colleagues explore the intricate co-evolutionary dynamics between fish and their parasites, describing an "arms race" in which helminths deploy potent immune evasion strategies while fish evolve increasingly sophisticated innate defenses. Their review details the pivotal role of innate immune cells, including mucous cells, mast cells, neutrophils, and macrophages, in response to parasite infections. These cells not only eliminate pathogens, but also orchestrate tissue repair and inflammatory modulation. Such findings highlight the complexity of host-parasite interactions and their implications for fish health management.From coelomocytes in echinoderms to macrophages in teleosts, aquatic species deploy a wide array of immune cells to combat pathogens and maintain homeostasis. Studies such as those by La Paglia and colleagues on Holothuria tubulosa reveal the proteomic complexity of coelomic fluid, identifying key proteins involved in phagocytosis, cytoskeletal remodeling, and signaling. Notably, the discovery of primary cilium-like structures in invertebrate immune cells provides novel insight into ancient, evolutionarily conserved immune signaling mechanisms. A recurring theme across taxa is the role of pattern recognition receptors (PRRs), particularly TLRs, in pathogen detection and immune activation. Ghani and colleagues provide a comprehensive review of TLRs, emphasizing their evolutionary divergence and categorization, 3D architecture, ligand recognition, signaling pathways, and expression dynamics during development. The review also highlights structural and functional differences between the TLRs of aquatic organisms and their mammalian counterparts, underscoring their unique roles in pathogen detection and adaptive immunological strategies in aquatic environments. Understanding these mechanisms offers promising strategies for aquaculture disease management and the development of targeted immunostimulants.Collectively, the contributions in this Research Topic challenge traditional views of innate immunity in aquatic organisms. From hemocytes in oysters to coelomocytes in echinoderms and RBCs in teleosts, these studies reveal a dynamic and multifaceted immune landscape shaped by evolutionary pressures and ecological demands. Beyond advancing fundamental knowledge, these insights lay the groundwork for translational applications in aquaculture, environmental monitoring, and evolutionary immunology.