Editors' ChoiceImmunology

Primed for inflammation by past meals

Sci. Signal.  28 Jun 2016:
Vol. 9, Issue 434, pp. ec149
DOI: 10.1126/scisignal.aah4253

In comparison with the adaptive immune system, the innate immune system, which includes macrophages, has been mostly thought to lack immunological memory. Weavers et al. showed that in Drosophila, engulfment of apoptotic corpses during development primed macrophages so that they were recruited to sites of tissue damage or infection in adulthood. Developmental apoptosis does not occur in H99 embryos because they lack three genes required for this process. Macrophages appeared to differentiate normally and migrate to the appropriate locations in H99 embryos during development. Moreover, they phagocytosed fluorescent beads and necrotic tissue if they happened to be located close to wound sites. However, macrophages in H99 embryos did not migrate to wound sites. This defect was rescued upon stimulation of apoptosis after UV exposure, which generated apoptotic corpses that were engulfed by the macrophages. Macrophage priming required frequent, transient increases in cytosolic calcium concentrations, which stimulated the activity of the kinase JNK and consequently an increase in the mRNA and protein abundance of the phagocytic receptor Draper. The mRNA and protein abundance of Draper was low in naïve wild-type embryos before corpse uptake or in H99 embryos not exposed to UV irradiation. Overexpression of Draper in H99 embryos enabled the recruitment of macrophages to wound sites. In addition to their inability to migrate to wound sites, H99 macrophages did not phagocytose E. coli, a defect that was rescued after UV-induced stimulation of apoptosis or ectopic expression of Draper. Similar to the signaling requirements for migration to wound sites, phagocytosis of E. coli in wild-type macrophages required cytosolic calcium increases and JNK signaling. Thus, phagocytosis of apoptotic corpses during development produces an immunological memory mediated by increased Draper abundance that enables macrophages to migrate to sites of injury or infection.

H. Weavers, I. R. Evans, P. Martin, W. Wood, Corpse engulfment generates a molecular memory that primes the macrophage inflammatory response. Cell 165, 1658–1671 (2016). [PubMed]

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