title: Bee venom phospholipase A2 induces a primary type 2 response that is dependent on the receptor ST2 and confers protective immunity.
abstract: Venoms consist of toxic components that are delivered to their victims via bites or stings. Venoms also represent a major class of allergens in humans. Phospholipase A2 (PLA2) is a conserved component of venoms from multiple species and is the major allergen in bee venom. Here we examined how bee venom PLA2 is sensed by the innate immune system and induces a type 2 immune response in mice. We found that bee venom PLA2 induced a T helper type 2 (Th2) cell-type response and group 2 innate lymphoid cell activation via the enzymatic cleavage of membrane phospholipids and release of interleukin-33. Furthermore, we showed that the IgE response to PLA2 could protect mice from future challenge with a near-lethal dose of PLA2. These data suggest that the innate immune system can detect the activity of a conserved component of venoms and induce a protective immune response against a venom toxin.
authors.affiliation: Howard Hughes Medical Institute, Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Noah W
authors.initials: NW
authors.lastname: Palm
authors.forename: Rachel K
authors.initials: RK
authors.lastname: Rosenstein
authors.forename: Shuang
authors.initials: S
authors.lastname: Yu
authors.forename: Dominik D
authors.initials: DD
authors.lastname: Schenten
authors.forename: Esther
authors.initials: E
authors.lastname: Florsheim
authors.forename: Ruslan
authors.initials: R
authors.lastname: Medzhitov
mesh_terms: D000707:Anaphylaxis / Q000209:etiology / Q000276:immunology / Q000517:prevention & control; D000818:Animals; D001514:Bee Venoms / Q000201:enzymology* / Q000633:toxicity; D003435:Crotalid Venoms / Q000276:immunology; D017930:Genes, Reporter; D007113:Immunity, Innate / Q000276:immunology*; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D019476:Insect Proteins / Q000276:immunology*; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics; D007378:Interleukins / Q000276:immunology; D008213:Lymphocyte Activation; D008246:Lysophospholipids / Q000276:immunology*; D008555:Melitten / Q000276:immunology; D008563:Membrane Lipids / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency / Q000502:physiology; D010047:Ovalbumin / Q000276:immunology; D054467:Phospholipases A2 / Q000276:immunology*; D010743:Phospholipids / Q000378:metabolism; D017455:Receptors, IgE / Q000276:immunology; D018123:Receptors, Interleukin / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D001514:Bee Venoms; D003435:Crotalid Venoms; C486189:Il1rl1 protein, mouse; C506535:Il33 protein, mouse; D007074:Immunoglobulin G; D019476:Insect Proteins; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins; D008246:Lysophospholipids; D008563:Membrane Lipids; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D010743:Phospholipids; D017455:Receptors, IgE; D018123:Receptors, Interleukin; D008555:Melitten; D015847:Interleukin-4; D007073:Immunoglobulin E; D010047:Ovalbumin; D054467:Phospholipases A2