title: Distinct immune effector pathways contribute to the full expression of peanut-induced anaphylactic reactions in mice.
abstract: BACKGROUND
  Food-induced anaphylaxis is often a severe allergic reaction characterized by multiorgan dysfunction and a potentially fatal outcome.
  
  
  OBJECTIVE
  We sought to investigate the relative contribution of immunoglobulin-dependent effector pathways to anaphylactic responses to food (ie, peanut).
  
  
  METHODS
  Wild-type and various mutant mice were sensitized with peanut protein and cholera toxin by means of oral gavage weekly for 4 weeks. Mice were subjected to different cellular depletion and Fc receptor blocking strategies before challenge with peanut 1 week after the last sensitization.
  
  
  RESULTS
  Our data indicate that pathways other than the classical mast cell (MC)-IgE pathway contribute to the full spectrum of anaphylactic reactions to peanut. We show that the single deletion of MCs, basophils, or phagocytes (ie, macrophages) prevents the most significant clinical outcome: death. Remarkably, the combined deficiency of MCs and phagocytes, but not MCs and basophils, averted nearly all clinical and physiological signs of anaphylaxis. Furthermore, blockade of both IgE and IgG1 signaling was necessary to abolish anaphylactic responses to peanut. Although MC responses occurred through IgE and IgG1, phagocyte responses were fully mediated through IgG1.
  
  
  CONCLUSIONS
  Peanut-induced anaphylaxis is a process that involves the concerted action of multiple immune effector pathways, and thus interventions targeting a single pathway (eg, MC-IgE) might not be sufficient to fully prevent anaphylactic responses.
authors.affiliation: Department of Pathology and Molecular Medicine, Centre for Gene Therapeutics, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Katherine
authors.initials: K
authors.lastname: Arias
authors.forename: Derek K
authors.initials: DK
authors.lastname: Chu
authors.forename: Kristin
authors.initials: K
authors.lastname: Flader
authors.forename: Fernando
authors.initials: F
authors.lastname: Botelho
authors.forename: Tina
authors.initials: T
authors.lastname: Walker
authors.forename: Natalia
authors.initials: N
authors.lastname: Arias
authors.forename: Alison A
authors.initials: AA
authors.lastname: Humbles
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Coyle
authors.forename: Hans C
authors.initials: HC
authors.lastname: Oettgen
authors.forename: Hyun-Dong
authors.initials: HD
authors.lastname: Chang
authors.forename: Nico
authors.initials: N
authors.lastname: Van Rooijen
authors.forename: Susan
authors.initials: S
authors.lastname: Waserman
authors.forename: Manel
authors.initials: M
authors.lastname: Jordana
mesh_terms: D000707:Anaphylaxis / Q000209:etiology / Q000276:immunology* / Q000517:prevention & control; D000818:Animals; D001491:Basophils / Q000276:immunology; D005260:Female; D007073:Immunoglobulin E / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D008264:Macrophages / Q000276:immunology; D008407:Mast Cells / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D021183:Peanut Hypersensitivity / Q000209:etiology / Q000276:immunology*; D017452:Receptors, IgG / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology
chemical_list: D007074:Immunoglobulin G; D017452:Receptors, IgG; D007073:Immunoglobulin E