Phagosome Maturation in Macrophages is Enhanced by p38α MAPK Signaling

Abstract It is generally assumed that without active escape mechanisms, all cargo phagocytosed by macrophages eventually reaches lysosomes. Yet, the influence of specific ligands present on the cargo, like lipopolysaccharide (LPS), on phagosome maturation is unclear. Using sterile, non‐immunogenic particles as model cargo phagocytosed by macrophages, this study showed that in the absence of a specific ligand on the cargo, less than half the cargo‐loaded phagosomes fuse with lysosomes. Quantification of phagosome maturation revealed that early events triggered by LPS‐induced signaling enhance both cargo delivery to lysosomes and phagosome acidification rates. Specifically, it is demonstrated that stress‐activated p38 alpha mitogen‐activated protein kinase (p38 MAPK) enhances phagosome maturation under LPS‐triggered signaling. Other signals known to activate p38 MAPK such as flagellin, IgG, and albumin, also enhance lysosomal delivery of phagocytosed cargo. The work indicates that phagosome maturation in macrophages is enhanced by specific ligands on the cargo, which activate cell surface receptors that signal via p38 MAPK.