Identification of Two Distinct Mechanisms of Phagocytosis Controlled by Different Rho GTPases

TLDR

Complement and immunoglobulin receptors are the main phagocytic receptors, but only immunoglobulin‑dependent uptake triggers a respiratory burst and inflammatory response in macrophages. Rho GTPases are essential for both phagocytic pathways, with Cdc42/Rac mediating immunoglobulin receptor–driven Type I phagocytosis and Rho mediating complement receptor–driven Type II, explaining the distinct biological outcomes.

Abstract

The complement and immunoglobulin receptors are the major phagocytic receptors involved during infection. However, only immunoglobulin-dependent uptake results in a respiratory burst and an inflammatory response in macrophages. Rho guanosine triphosphatases (molecular switches that control the organization of the actin cytoskeleton) were found to be essential for both types of phagocytosis. Two distinct mechanisms of phagocytosis were identified: Type I, used by the immunoglobulin receptor, is mediated by Cdc42 and Rac, and type II, used by the complement receptor, is mediated by Rho. These results suggest a molecular basis for the different biological consequences that are associated with phagocytosis.