Analysis of receptor-ligand pairings and distribution of myeloid subpopulations across the animal kingdom reveals neutrophil evolution was facilitated by colony-stimulating factors

Abstract

AbstractNeutrophils or heterophils constitute the largest population of phagocytic granulocytes in the blood of mammals and birds. The development and function of neutrophils and monocytes is primarily governed by the granulocyte colony-stimulating factor receptor family (CSF3R/CSF3) and macrophage colony-stimulating factor receptor family (CSF1R/IL34/CSF1) respectively. Using various techniques this study considered how the emergence of receptor:ligand pairings shaped the distribution of blood myeloid cell populations. Comparative gene analysis supported the ancestral pairings of CSF1R/IL34 and CSF3R/CSF3, and the emergence of CSF1 later in tetrapod lineages after the advent of Jawed/Jawless fish. Further analysis suggested that the emergence of CSF3 lead to reorganisation of granulocyte distribution between amphibian and early reptiles. However, the advent of endothermy likely contributed to the dominance of the neutrophil/heterophil in modern-day mammals and birds. In summary, we show that the emergence of CSF3R/CSF3 was a key factor in the subsequent evolution of the modern-day mammalian neutrophil.Impact statementColony-stimulating factors (CSFs) are important for myeloid phagocyte development. The emergence of CSF3/CSF3R in tetrapod lineages has uniquely contributed to physical, functional and structural adaptions observed in mammalian neutrophils.