Critical role of the neutrophil-associated high-affinity receptor for IgE in the pathogenesis of experimental cerebral malaria

• DOI: 10.1084/jem.20110845
• Publication Date: 2011-10-04T03:24:31Z
• Authors: Adeline Porcherie; Cedric Mathieu; Roger Peronet; Elke Schneider; Julien Claver; Pierre-Henri Commere; Hélène Kiefer-Bia...; Hajime Karasuyama; Geneviève Milon; Michel Dy; Jean-Pierre Kinet; Jacques Louis; Ulrich Blank; Salaheddine Mécheri
• Keywords: Mice, Knockout; 0301 basic medicine; [SDV.IMM] Life Sciences [q-bio]/Immunology; Neutrophils; Plasmodium berghei; Receptors, IgE; Malaria, Cerebral; Immunoglobulin E; Adoptive Transfer; Article; Basophils; 3. Good health; Eosinophils; Mice, Inbred C57BL; Mice; 03 medical and health sciences; [SDV.IMM]Life Sciences [q-bio]/Immunology; Animals; Cytokines; Protein Isoforms; Female

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.