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1. Amphibian myelopoiesis

   https://doi.org/10.1016/j.dci.2023.104701  

   Yaparla A, Stern DB (January 2023, Developmental and comparative immunology)

   Brian Dixon (Ed.)

   Macrophage-lineage cells are indispensable to immunity and physiology of all vertebrates. Amongst these, amphibians represent a key stage in vertebrate evolution and are facing decimating population declines and extinctions, in large part due to emerging infectious agents. While recent studies indicate that macrophages and related innate immune cells are critically involved during these infections, much remains unknown regarding the ontogeny and functional differentiation of these cell types in amphibians. Accordingly, in this review we coalesce what has been established to date about amphibian blood cell development (hematopoiesis), the development of key amphibian innate immune cells (myelopoiesis) and the differentiation of amphibian macrophage subsets (monopoiesis). We explore the current understanding of designated sites of larval and adult hematopoiesis across distinct amphibian species and consider what mechanisms may lend to these species-specific adaptations. We discern the identified molecular mechanisms governing the functional differentiation of disparate amphibian (chiefly Xenopus laevis) macrophage subsets and describe what is known about the roles of these subsets during amphibian infections with intracellular pathogens. Macrophage lineage cells are at the heart of so many vertebrate physiological processes. Thus, garnering greater understanding of the mechanisms responsible for the ontogeny and functionality of these cells in amphibians will lend to a more comprehensive view of vertebrate evolution. 

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2. Amphibian (Xenopus laevis) Macrophage Subsets Vary in Their Responses to the Chytrid Fungus Batrachochytrium dendrobatidis

   https://doi.org/10.3390/jof11040311  

   Yaparla, Amulya; Popovic, Milan; Hauser, Kelsey A; Rollins-Smith, Louise A; Grayfer, Leon (April 2025, Journal of Fungi)

   The chytrid fungus, Batrachochytrium dendrobatidis (Bd), infects amphibian skin, causing chytridiomycosis, which is a contributing cause of worldwide declines and extinctions of amphibians. Relatively little is known about the roles of amphibian skin-resident immune cells, such as macrophages, in these antifungal defenses. Across vertebrates, macrophage differentiation is controlled through the activation of colony-stimulating factor-1 (CSF1) receptor by CSF1 and interleukin-34 (IL34) cytokines. While the precise roles of these respective cytokines in macrophage development remain to be fully explored, our ongoing studies indicate that frog (Xenopus laevis) macrophages differentiated by recombinant forms of CSF1 and IL34 are functionally distinct. Accordingly, we explored the roles of X. laevis CSF1- and IL34-macrophages in anti-Bd defenses. Enriching cutaneous IL34-macrophages, but not CSF1-macrophages, resulted in significant anti-Bd protection. In vitro analysis of frog macrophage-Bd interactions indicated that both macrophage subsets phagocytosed Bd. However, IL34-macrophages cocultured with Bd exhibited greater pro-inflammatory gene expression, whereas CSF1-macrophages cocultured with Bd showed greater immunosuppressive gene expression profiles. Concurrently, Bd-cocultured with CSF1-macrophages, but not IL34-macrophages, possessed elevated expression of genes associated with immune evasion. This work marks a step forward in our understanding of the roles of frog macrophage subsets in antifungal defenses. 

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3. Immune evasion by a chytrid fungus includes inhibition of macrophage phagocytosis

   https://doi.org/10.1128/iai.00591-25  

   Rollins-Smith, Louise A; Le_Sage, Mitchell; Simoneau, Chelsea Roach; Singh, Somya; Hossainey, Muhammad_Riadul Haque; Serezani, Carlos Henrique; Grayfer, Leon (May 2026, Infection and Immunity)

   Zhang, Jingren (Ed.)

   ABSTRACT Batrachochytrium dendrobatidiscontinues to cause declines in amphibian populations worldwide, and it remains unclear why skin defenses often fail to control the infection. Although amphibians have a complex, multifunctional immune system, the chytridiomycosis agent seems to have evolved countermeasures that enable it to survive and eventually impair critical skin functions. Previous studies show thatB. dendrobatidiscells or cell-free supernatants inhibit lymphocytes by inducing apoptosis, suggesting impaired local cell killing. However, there is little evidence of lymphocyte recruitment to chytrid-infected skin, implying the fungus may also inhibit the functions of antigen-presenting cells. Here, we demonstrate that phagocytosis by peritoneal macrophages is significantly reduced by co-culture with live or heat-killedB. dendrobatidiszoosporangia, freeze-thawed zoospores, fungal cell-free supernatants, or cell-wall fragments. The phagocytic capacity of frog bone marrow-derived macrophages, differentiated by colony-stimulating factor-1 (CSF-1) or interleukin-34 (IL-34) (key macrophage growth factors), as well as immortalized mammalian macrophages, is also impaired. Inhibition of mammalian macrophages suggests that these inhibitory factors are not restricted to amphibian cells. Overall, these studies indicate thatB. dendrobatidiscells and their components can hinder the recognition and function of macrophages that reside in or enter the skin to clear infections. This disabling of host phagocytosis is undoubtedly central to howB. dendrobatidisprevents effective innate and adaptive immune responses in the skin. 

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4. Xenopus Interferon Complex: Inscribing the Amphibiotic Adaption and Species-Specific Pathogenic Pressure in Vertebrate Evolution?

   https://doi.org/10.3390/cells9010067  

   Tian, Yun; Jennings, Jordan; Gong, Yuanying; Sang, Yongming (January 2020, Cells)

   Several recent studies have revealed previously unknown complexity of the amphibian interferon (IFN) system. Being unique in vertebrate animals, amphibians not only conserve and multiply the fish-like intron-containing IFN genes, but also rapidly evolve amniote-like intronless IFN genes in each tested species. We postulate that the amphibian IFN system confers an essential model to study vertebrate immune evolution in molecular and functional diversity to cope with unprecedented pathophysiological requirement during terrestrial adaption. Studies so far have ascribed a potential role of these IFNs in immune regulation against intracellular pathogens, particularly viruses; however, many knowledge gaps remain elusive. Based on recent reports about IFN’s multifunctional properties in regulation of animal physiological and defense responses, we interpret that amphibian IFNs may evolve novel function pertinent to their superior molecular diversity. Such new function revealed by the emerging studies about antifungal and developmental regulation of amphibian IFNs will certainly promote our understanding of immune evolution in vertebrates to address current pathogenic threats causing amphibian decline. 

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5. Still Enigmatic: Innate Immunity in the Ctenophore Mnemiopsis leidyi

   https://doi.org/10.1093/icb/icz116  

   Traylor-Knowles, Nikki; Vandepas, Lauren E; Browne, William E (August 2019, Integrative and Comparative Biology)

   Abstract Innate immunity is an ancient physiological response critical for protecting metazoans from invading pathogens. It is the primary pathogen defense mechanism among invertebrates. While innate immunity has been studied extensively in diverse invertebrate taxa, including mollusks, crustaceans, and cnidarians, this system has not been well characterized in ctenophores. The ctenophores comprise an exclusively marine, non-bilaterian lineage that diverged early during metazoan diversification. The phylogenetic position of ctenophore lineage suggests that characterization of the ctenophore innate immune system will reveal important features associated with the early evolution of the metazoan innate immune system. Here, we review current understanding of the ctenophore immune repertoire and identify innate immunity genes recovered from three ctenophore species. We also isolate and characterize Mnemiopsis leidyi cells that display macrophage-like behavior when challenged with bacteria. Our results indicate that ctenophores possess cells capable of phagocytosing microbes and that two distantly related ctenophores, M. leidyi and Hormiphora californiensis, possess many candidate innate immunity proteins. 

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