title: p38 MAPK-dependent phagocytic encapsulation confers infection tolerance in Drosophila.
abstract: Hosts employ a combination of two distinct yet compatible strategies to defend themselves against parasites: resistance, the ability to limit parasite burden, and tolerance, the ability to limit damage caused by a given parasite burden. Animals typically exhibit considerable genetic variation in resistance to a variety of pathogens; however, little is known about whether animals can evolve tolerance. Using a bacterial infection model in Drosophila, we uncovered a p38 MAP kinase-mediated mechanism of tolerance to intracellular bacterial infection as measured by the extent to which the host's survival rate increased or was maintained despite increasing bacterial burden. This increased survival was conferred primarily by a tolerance strategy whereby p38-dependent phagocytic encapsulation of bacteria resulted in enlarged phagocytes that trap bacteria. These results suggest that phagocytic responses are not restricted to resistance mechanisms but can also be applied to tolerance strategies for intracellular encapsulation of pathogens during the invertebrate immune response.
authors.affiliation: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido, Japan.
authors.forename: Naoaki
authors.initials: N
authors.lastname: Shinzawa
authors.forename: Bryce
authors.initials: B
authors.lastname: Nelson
authors.forename: Hiroka
authors.initials: H
authors.lastname: Aonuma
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Okado
authors.forename: Shinya
authors.initials: S
authors.lastname: Fukumoto
authors.forename: Masayuki
authors.initials: M
authors.lastname: Miura
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Kanuka
mesh_terms: D000818:Animals; D004330:Drosophila / Q000235:genetics / Q000276:immunology* / Q000382:microbiology*; D029721:Drosophila Proteins / Q000235:genetics / Q000276:immunology*; D005260:Female; D006434:Hemocytes / Q000276:immunology / Q000382:microbiology; D054884:Host-Pathogen Interactions; D007108:Immune Tolerance; D008089:Listeria monocytogenes / Q000502:physiology; D008297:Male; D010587:Phagocytosis; D012486:Salmonella typhimurium / Q000502:physiology; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000276:immunology*
chemical_list: D029721:Drosophila Proteins; D048051:p38 Mitogen-Activated Protein Kinases