Cell165, 1658-1671(2016)
Macrophages are multifunctional cells, the main roles of them are phagocytosis and clearance of dying apoptotic cells during normal development/tissue homeostasis and at sites of inflammation. Paul Martinand Will Woodat University of Bristol, UK andtheirco-workers combined development with inflammation, usingDrosophilaembryo, a easily real-time observing and precisely manipulating model, to investigate macrophage priming and phenotypic plasticity responsing to stimuli.
The researchs foundmutant embryos’s lack of programmed cell death caused macrophages kept“naive”without large intracellular vacuoles formed during engulfing apoptotic corpses like wild-type cells.“naive”macrophages failed to accumulate at the wound site, however, UV induced apoptosis led to corpse phagocytosis and then recover the wound inflammatory response, which showed that corpse phagocytosis is an essential step to prime macrophages for a robust inflammatory recruitment to wounds and uptake of bacteria.
Such macrophages primingis triggered by amolecular memory, up-regulated damage receptor Draper, which allows the cell to rapidly respond to subsequent injury or infection. The increased expression of Draper was a result of calcium-induced JNK signaling, and calcium burst appeared in the apoptosis corpse.
Previous studies focus on macrophage reprogramming after infection, called trained innate immunity, this research give us new view of apoptosis memory storage in individual macrophage cell can trigger the innate inflammatory to where extensive apoptotic cell death in inflamed sites.
The researches considered understanding the remarkable plasticity and capacity for memory of macrophages will shed light on molecular mechanisms responsible for innate immune priming and finally target therapeutic treatment of inflammatory disorders.
