title: Corpse Engulfment Generates a Molecular Memory that Primes the Macrophage Inflammatory Response.
abstract: 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.
authors.affiliation: Department of Biochemistry, Biomedical Sciences, University of Bristol, Bristol BS8 1TD, UK; Department of Cellular and Molecular Medicine, Biomedical Sciences, University of Bristol, Bristol BS8 1TD, UK.
authors.forename: Helen
authors.initials: H
authors.lastname: Weavers
authors.affiliation: Department of Infection, Immunity and Cardiovascular Disease and the Bateson Centre, University of Sheffield, Sheffield S10 2TN, UK.
authors.forename: Iwan R
authors.initials: IR
authors.lastname: Evans
authors.affiliation: Department of Biochemistry, Biomedical Sciences, University of Bristol, Bristol BS8 1TD, UK; Department of Physiology, Pharmacology and Neuroscience, Biomedical Sciences, University of Bristol, Bristol BS8 1TD, UK; School of Medicine, Cardiff University, Cardiff CF14 4XN, UK; Lee Kong Chiang School of Medicine, Nanyang Technologicial University, Singapore 636921, Singapore. Electronic address: paul.martin@bristol.ac.uk.
authors.forename: Paul
authors.initials: P
authors.lastname: Martin
authors.affiliation: Department of Cellular and Molecular Medicine, Biomedical Sciences, University of Bristol, Bristol BS8 1TD, UK. Electronic address: w.wood@bristol.ac.uk.
authors.forename: Will
authors.initials: W
authors.lastname: Wood
mesh_terms: D000818:Animals; D017209:Apoptosis; D004330:Drosophila / Q000166:cytology / Q000276:immunology*; D029721:Drosophila Proteins / Q000378:metabolism; D004926:Escherichia coli; D007113:Immunity, Innate; D007156:Immunologic Memory; D020935:MAP Kinase Signaling System; D008264:Macrophages / Q000276:immunology*; D008565:Membrane Proteins / Q000378:metabolism; D010587:Phagocytosis
chemical_list: D029721:Drosophila Proteins; D008565:Membrane Proteins; C495322:drpr protein, Drosophila