Corpse Engulfment Generates a Molecular Memory that Primes the Macrophage Inflammatory Response

Summary

Macrophages are multifunctional cells that perform diverse roles in health and disease. Emerging evidence has suggested that these innate immune cells might also be capable of developing immunological memory, a trait previously associated with the adaptive system alone. While recent studies have focused on the dramatic macrophage reprogramming that follows infection and protects against secondary microbial attack, can macrophages also develop memory in response to other cues? Here, we show that apoptotic corpse engulfment by Drosophila macrophages is an essential primer for their inflammatory response to tissue damage and infection in vivo. Priming is triggered via calcium-induced JNK signaling, which leads to upregulation of the damage receptor Draper, thus providing a molecular memory that allows the cell to rapidly respond to subsequent injury or infection. This remarkable plasticity and capacity for memory places macrophages as key therapeutic targets for treatment of inflammatory disorders.

Graphical Abstract

Highlights

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  Phagocytosis of apoptotic cells primes macrophages for future inflammatory response

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  Naive macrophages are insensitive to tissue damage and bacterial infection

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  Corpse uptake triggers macrophage calcium bursts that potentiate priming

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  Calcium-induced JNK primes macrophages by upregulating the damage receptor Draper

Abstract

Macrophages that consume apoptotic corpses during fly development become primed for inflammatory responses later in life, establishing a form of molecular memory that aids in the response to bacterial infection and tissue damage.