title: Critical role of the neutrophil-associated high-affinity receptor for IgE in the pathogenesis of experimental cerebral malaria.
abstract: The role of the IgE-FcεRI complex in malaria severity in Plasmodium falciparum-hosting patients is unknown. We demonstrate that mice genetically deficient for the high-affinity receptor for IgE (FcεRIα-KO) or for IgE (IgE-KO) are less susceptible to experimental cerebral malaria (ECM) after infection with Plasmodium berghei (PbANKA). Mast cells and basophils, which are the classical IgE-expressing effector cells, are not involved in disease as mast cell-deficient and basophil-depleted mice developed a disease similar to wild-type mice. However, we show the emergence of an FcεRI(+) neutrophil population, which is not observed in mice hosting a non-ECM-inducing PbNK65 parasite strain. Depletion of this FcεRI(+) neutrophil population prevents ECM, whereas transfer of this population into FcεRIα-KO mice restores ECM susceptibility. FcεRI(+) neutrophils preferentially home to the brain and induce elevated levels of proinflammatory cytokines. These data define a new pathogenic mechanism of ECM and implicate an FcεRI-expressing neutrophil subpopulation in malaria disease severity.
authors.affiliation: Institut Pasteur, Unité de Biologie des Interactions Hôte Parasites, Paris, France.
authors.forename: Adeline
authors.initials: A
authors.lastname: Porcherie
authors.forename: Cedric
authors.initials: C
authors.lastname: Mathieu
authors.forename: Roger
authors.initials: R
authors.lastname: Peronet
authors.forename: Elke
authors.initials: E
authors.lastname: Schneider
authors.forename: Julien
authors.initials: J
authors.lastname: Claver
authors.forename: Pierre-Henri
authors.initials: PH
authors.lastname: Commere
authors.forename: Hélène
authors.initials: H
authors.lastname: Kiefer-Biasizzo
authors.forename: Hajime
authors.initials: H
authors.lastname: Karasuyama
authors.forename: Geneviève
authors.initials: G
authors.lastname: Milon
authors.forename: Michel
authors.initials: M
authors.lastname: Dy
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Kinet
authors.forename: Jacques
authors.initials: J
authors.lastname: Louis
authors.forename: Ulrich
authors.initials: U
authors.lastname: Blank
authors.forename: Salaheddine
authors.initials: S
authors.lastname: Mécheri
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001491:Basophils / Q000166:cytology / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D004804:Eosinophils / Q000166:cytology / Q000276:immunology; D005260:Female; D007073:Immunoglobulin E / Q000235:genetics / Q000276:immunology*; D016779:Malaria, Cerebral / Q000276:immunology* / Q000469:parasitology / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000166:cytology / Q000276:immunology*; D010962:Plasmodium berghei / Q000276:immunology / Q000472:pathogenicity; D020033:Protein Isoforms / Q000235:genetics / Q000276:immunology; D017455:Receptors, IgE / Q000235:genetics / Q000276:immunology*
chemical_list: D016207:Cytokines; D020033:Protein Isoforms; D017455:Receptors, IgE; D007073:Immunoglobulin E