Evolutionary Origin of M2 Macrophage Activation: Invertebrates

Abstract

Phagocytic macrophage-like cells of invertebrates were the first immune cells ever studied scientifically. These cells are described as Amoeba-like (“amoeboid”) cells in the book by Thomas Huxley on invertebrate anatomy in 1878 [1]. In the 1880s, Ilya Metchnikoff [Илья Мечников] (1845–1916) carried out experiments on echinoderm, molluscan, and insect hemocytes [2, 3]. He noticed an encapsulation of foreign particles by amoeboid cells of the sea urchin larva, and eventually he conducted extensive studies on phagocytosing cells, which opened the avenue for the development of the theory of innate immunity. He was honored with the Nobel prize in 1908 [4]. Indeed, Metchnikoff postulated that metazoans have evolved from a common ancestor, a phagocytosing cell colony, which he termed as “Phagocytella” in 1886 [5, 6]. Another interesting hypothesis from Rudolf Virchow (1821–1902) and Ernst Haeckel (1834–1919) went even further: the first cells were probably formed by the aggregation of simple vesicles, and because Amoeba cells are rich in such vesicles, an Amoeba-like “Cytode,” or “Protamoeaba,” was the possible forefather of all cells [7, 8]. These theories are interesting pieces of science history today. However, macrophage-like cells are present in the simplest metazoans, and the Toll receptor, for instance, one of the most important pathogen recognition receptor of macrophages, was also initially identified in an invertebrate [9]. This chapter reviews how tolerogenic and growth-supporting macrophage traits, that is, M2 macrophage traits, have evolved in invertebrates.