Reactive oxygen species-mediated cytoplasmic stiffening impairs the phagocytic ability of the macrophage

The phagocytic ability of the macrophages empowers them to enforce innate immunity. The RAW264.7, THP-1 and PBMC derived macrophages display considerable variability in regards to their phagocytic ability. We identify the underlying causes that cripple a macrophage's phagocytic ability. Deformability of the cytoplasm/cortex influences the phagocytic ability, and macrophages use the large cell-to-cell variability of its cytoplasmic stiffness to modulate their phagocytic ability. We find that more deformable macrophages have a higher phagocytic ability. Further, the sub-cellular spatial variability of cortex stiffness gives rise to more deformable sub-domains on the membrane for pathogen ingestion. We report a previously unknown negative feedback loop that gets triggered by the phagocytic oxidative burst. Macrophages utilize the excess ROS to stiffen the cytoplasm, reducing their phagocytic propensity. In organisms, ageing or pathological conditions impairs the phagocytic ability of macrophages. Our findings identify the targets that could potentially be utilized for restoring the phagocytic ability of the defunct macrophages.