Chapter 4 : Evolution of Myeloid Cells

Abstract:

The drive to clear dying cells is evident even in the deepest branches of the Archaea and Bacteria phylogeny, where colonial biofilms appeared as a mode to promote survival in diverse environments ( 1 ). These ancient colonies (earliest fossil record ∼3.25 billion years ago) already displayed attributes of multicellular organism specialization, removing nonfunctional spent cells to recycle nutrients and maintain the integrity of the colony ( 1 , 2 ). Multicellularity followed shortly after and introduced a requirement for removal of nonself ( 3 , 4 ). Phagocytosis provided an elegant answer to both challenges, and has since served as a primary tool for cell turnover and removal of foreign invaders across all animal groups. It therefore provides a good stage to examine the evolution of myeloid cells through their contributions to homeostasis and host defenses ( Fig. 1 ). This chapter first focuses on ancestral phagocytes and examines their progression from primarily homeostatic cells to multifaceted effectors and regulators of immunity. The literature provides some insight into macrophage and lower metazoan hemocyte function as far back as echinoderms and urochordates. Further examination of gene marker conservation (e.g., apoptotic genes) in sponges and other colonial organisms allows us to dig deeper to examine the factors that led to the phylogenetic origins of cell clearance mechanisms and their continued evolution across newly developing animal branches. Subsequently, we focus on key challenges encountered by higher vertebrate myeloid cells as they manage increasingly complex mechanisms of immunity while maintaining a strict balance between proinflammatory and homeostatic cellular responses. In one example, we examine the impact of specialization through the diverging contributions of macrophages and neutrophils. We then consider the continued specialization of the myeloid lineage through the eyes of the dendritic cell (DC), which, through antigen presentation, effectively integrated new adaptive features into well-established and robust innate mechanisms of immunity. Indeed, documenting the multiple facets that comprise the life history of myeloid cells across evolution would not be possible in a single chapter. However, by focusing on their origins as phagocytes, we can appreciate the continued struggle of a host to develop novel and effective strategies to combat invading pathogens while ensuring the continued maintenance of tissue integrity and homeostasis.