Amphibian macrophage development and antiviral defenses

Abstract

Macrophage lineage cells represent the cornerstone of vertebrate physiology and immune defenses. In turn, comparative studies using non-mammalian animal models have revealed that evolutionarily distinct species have adopted diverse molecular and physiological strategies for controlling macrophage development and functions. Notably, amphibian species present a rich array of physiological and environmental adaptations, not to mention the peculiarity of metamorphosis from larval to adult stages of development, involving drastic transformation and differentiation of multiple new tissues. Thus it is not surprising that different amphibian species and their respective tadpole and adult stages have adopted unique hematopoietic strategies. Accordingly and in order to establish a more comprehensive view of these processes, here we review the hematopoietic and monopoietic strategies observed across amphibians, describe the present understanding of the molecular mechanisms driving amphibian, an in particular Xenopus laevis macrophage development and functional polarization, and discuss the roles of macrophage-lineage cells during ranavirus infections.

Evolutionary Aspects of Macrophages Polarization

“…Compared to adult macrophages, a subset of tadpole macrophages is enlarged with a highly vacuolated morphology (Grayfer et al 2012). Although hematopoiesis in Xenopus is localized to the subcapsular liver, macrophage precursors in X. laevis, unlike other vertebrates, are derived from the bone marrow [(Grayfer and Robert 2013) and reviewed in (Grayfer and Robert 2016)]. Since the bone marrow is absent in tadpoles, it is currently unknown how tadpole macrophage development and differentiation occurs.…”

“…As the embryonic origin, lineage commitment and monopoiesis are considered in another chapter of this book, and amphibian myelopoiesis has recently been discussed in detail in (Grayfer and Robert 2016), this chapter will focus on the current understanding of the functional diversification potential of macrophages from an evolutionary perspective. We will particularly discuss comparative approaches aimed at defining macrophage plasticity in genetically distant species in bony fish and amphibians.…”

Xenopus-FV3 host-pathogen interactions and immune evasion

“…Compared to mammals where many types of tissue resident and circulating macrophages have been identified, the understanding of distinct macrophage subsets in cold blooded vertebrates, including Xenopus , is limited. However, monopoiesis is fundamentally conserved between amphibians and mammals (reviewed in (Grayfer and Robert, 2016; Huber and Zon, 1998; Robert and Ohta, 2009)). Macrophages reside in most organs and tissues throughout the amphibian body, where they provide a core foundation of the first line of host immune defenses against infectious agents such as ranavirus.…”

“…Macrophages reside in most organs and tissues throughout the amphibian body, where they provide a core foundation of the first line of host immune defenses against infectious agents such as ranavirus. Indeed, macrophages play a key role in orchestrating antiviral immunity against FV3 (Grayfer and Robert, 2016). Notably, the macrophage-colony stimulating factor (CSF) receptor 1 (CSF-R1) that drives the differentiation and function of macrophages was shown to interact in Xenopus as in mammals, with two distinct, evolutionarily unrelated ligands, CSF-1 and Interleukin 34 (IL-34; (Grayfer et al, 2014b)).…”

“…This functional disparity is of particular relevance since macrophages are not only crucial antiviral effector cells but appear to be specially targeted by ranavirus pathogens in Xenopus and other species including mammals (Gendrault et al, 1981; Grayfer and Robert, 2016; Gut et al, 1981). Considering the indiscriminate infection mode and apparent absence of specific cellular receptor(s) requirement, we have proposed that macrophages with their ability to acquire exogenous particles and antigens through various pathways such as micropinocytosis and phagocytosis represent an advantageous cellular target for viral dissemination and persistence into the host.…”