Phagocytosis: Hungry, Hungry Cells

Abstract

Phagocytosis is the cellular internalization and sequestration of particulate matter into a `phagosome, which then matures into a phagolysosome. The phagolysosome then offers a specialized acidic and hydrolytic milieu that ultimately degrades the engulfed particle. In multicellular organisms, phagocytosis and phagosome maturation play two key physiological roles. First, phagocytic cells have an important function in tissue remodeling and homeostasis by eliminating apoptotic bodies, senescent cells and cell fragments. Second, phagocytosis is a critical weapon of the immune system, whereby cells like macrophages and neutrophils hunt and engulf a variety of pathogens and foreign particles. Not surprisingly, pathogens have evolved mechanisms to either block or alter phagocytosis and phagosome maturation, ultimately usurping the cellular machinery for their own survival. Here, we review past and recent discoveries that highlight how phagocytes recognize target particles, key signals that emanate after phagocyte-particle engagement, and how these signals help modulate actin-dependent remodeling of the plasma membrane that culminates in the release of the phagosome. We then explore processes related to early and late stages of phagosome maturation, which requires fusion with endosomes and lysosomes. We end this review by acknowledging that little is known about phagosome fission and even less is known about how phagosomes are resolved after particle digestion.

Chemotherapy-induced senescent cancer cells engulf other cells to enhance their survival

“…Apoptotic cells are often engulfed not just by “professional” phagocytes such as macrophages, but also by other, nonprofessional phagocytic cell types as well (Gray and Botelho, 2017). Our observations and previous experiments using proliferating breast cancer cell cultures suggested a very low apoptotic rate.…”

Research progress on the immune mechanism of the silkworm Bombyx mori

“…In addition to the immune mechanisms described above, phagocytosis, a evolutionarily conservative immune mechanism, commonly exists in invertebrates and can remove the invasive pathogens and apoptotic residues (Lü, 2008;Ye et al, 2012;Chen et al, 2015). This process is accomplished in a single cell, involving the identification, phagocytosis, destruction of invasive pathogens and death of cells themselves (Williams, 2007;Gray & Botelho, 2017;Rashidfarrokhi et al, 2017). Meanwhile, PGRPs, βGRPs, lysozyme, hemolin and lectins also play important roles in the innate immunity of the silkworm (Ochiai & Ashida, 1988Lee & Brey, 1995;Yoshida et al, 1996;Gandhe et al, 2007).…”

Chemotactic network responses to live bacteria show independence of phagocytosis from chemoreceptor sensing

“…Particle interaction at the cell surface induces an actin re-organization, forming a cup in the plasma membrane that surrounds the particle for engulfment and re-direction to lysosomes for degradation. The shared mechanisms also underscore the great utility for model studies of host-pathogen interactions, where cells of the mammalian immune system and Dictyostelium exhibit similar susceptibility to virulence infection by Legionella pneumophila , Mycobacterium tuberculosis , and Listeria monocytogenes (Bozzaro et al, 2008; Steinert, 2011; Levin et al, 2016; Gray and Botelho, 2017). …”

“…Finally, we considered if chemotactic cell surface receptor signaling via pseudopod extension mediates phagocytosis through locally enhanced host-bacterial interactions (Swanson and Baer, 1995; Bozzaro et al, 2008; Heinrich and Lee, 2011; Levin et al, 2016; Niedergang et al, 2016; Gray and Botelho, 2017). Utilizing strains lacking or expressing specific chemoattractant GPCRs, we demonstrate that phagocytosis is minimally dependent on bacterial chemoattractant sensing; GPCR-deficient lines exhibit similar high efficiencies for phagocytosis as do corresponding strains that express WT (wild-type) GPCRs, regardless of their ability to respond chemotactically.…”