Schematic overview of main findings. Cartoons demonstrating the main findings described in the study. (left) Neutrophils may commit to phagocytosis or NETosis based on environmental triggers, in particular TLR activation. (right) Depiction of key signaling events resulting in TLR-mediated regulation of IC-mediated inflammation by neutrophils, monocytes, and pDCs. In brief, TLR activation results in activation of PI3K, contributing to generation of reactive oxygen species (ROS) via NADPH oxidase. ROS is essential for NET formation but also release of proteases able to shed FcgRIIA from immune cells. Loss of FcgRIIA results in increased ability of neutrophils to undergo IC-mediated NETosis, whereas also impairing phagocytic ability in neutrophils, monocytes, and pDCs. Noncleared ICs will instead activate the complement system to generate the anaphylatoxin C5a and be cleared through complement-dependent pathways.