Phagocytosis without inflammation

The rare brain disorder Nasu-Hakola disease is a fatal neurodegenerative syndrome that has been linked to mutations in immune signaling proteins, but the mechanism had not been explored. In a study on page 647, Takahashi et al. connect this disease to defects in phagocytic cells that are required for removal of apoptotic cells and suppression of inflammation in the brain.

The link to disease involves the TREM2 (triggering receptor expressed on myeloid cells-2) receptor and its associated adaptor protein DAP12, both known to be mutated in patients with Nasu-Hakola disease. TREMs are orphan receptors that associate with DAP12 to transmit signals in a variety of myeloid cells. The signals are primarily stimulatory: TREM1 signaling activates macrophages and neutrophils and can amplify Toll-like receptor signals, and TREM2 activates immature dendritic cells. TREM2 is also...