Bee venom phospholipase A2 induces a primary type 2 response that is dependent on the receptor ST2 and confers protective immunity

Immunity. 2013 Nov 14;39(5):976-85. doi: 10.1016/j.immuni.2013.10.006. Epub 2013 Oct 24.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anaphylaxis / etiology
  • Anaphylaxis / immunology
  • Anaphylaxis / prevention & control
  • Animals
  • Bee Venoms / enzymology*
  • Bee Venoms / toxicity
  • Crotalid Venoms / immunology
  • Genes, Reporter
  • Immunity, Innate / immunology*
  • Immunoglobulin E / biosynthesis*
  • Immunoglobulin E / immunology
  • Immunoglobulin G / biosynthesis
  • Immunoglobulin G / immunology
  • Insect Proteins / immunology*
  • Interleukin-1 Receptor-Like 1 Protein
  • Interleukin-33
  • Interleukin-4 / biosynthesis
  • Interleukin-4 / genetics
  • Interleukins / immunology
  • Lymphocyte Activation
  • Lysophospholipids / immunology*
  • Melitten / immunology
  • Membrane Lipids / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Myeloid Differentiation Factor 88 / deficiency
  • Myeloid Differentiation Factor 88 / physiology
  • Ovalbumin / immunology
  • Phospholipases A2 / immunology*
  • Phospholipids / metabolism
  • Receptors, IgE / immunology
  • Receptors, Interleukin / immunology*
  • Th2 Cells / immunology*

Substances

  • Bee Venoms
  • Crotalid Venoms
  • Il1rl1 protein, mouse
  • Il33 protein, mouse
  • Immunoglobulin G
  • Insect Proteins
  • Interleukin-1 Receptor-Like 1 Protein
  • Interleukin-33
  • Interleukins
  • Lysophospholipids
  • Membrane Lipids
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • Phospholipids
  • Receptors, IgE
  • Receptors, Interleukin
  • Melitten
  • Interleukin-4
  • Immunoglobulin E
  • Ovalbumin
  • Phospholipases A2