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

• Published in: The Journal of experimental medicine Vol. 208; no. 11; pp. 2225 - 2236
• Main Authors: Porcherie, Adeline, Mathieu, Cedric, Peronet, Roger, Schneider, Elke, Claver, Julien, Commere, Pierre-Henri, Kiefer-Biasizzo, Hélène, Karasuyama, Hajime, Milon, Geneviève, Dy, Michel, Kinet, Jean-Pierre, Louis, Jacques, Blank, Ulrich, Mécheri, Salaheddine
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 24.10.2011; The Rockefeller University Press
• Subjects: Adoptive Transfer; Animals; Basophils - cytology; Basophils - immunology; Cytokines - immunology; Eosinophils - cytology; Eosinophils - immunology; Female; Immunoglobulin E - genetics; Immunoglobulin E - immunology; Immunology; Life Sciences; Malaria, Cerebral - immunology; Malaria, Cerebral - parasitology; Malaria, Cerebral - pathology; Mice; Mice, Inbred C57BL; Mice, Knockout; Neutrophils - cytology; Neutrophils - immunology; Plasmodium berghei; Plasmodium berghei - immunology; Plasmodium berghei - pathogenicity; Protein Isoforms - genetics; Protein Isoforms - immunology; Receptors, IgE - genetics; Receptors, IgE - immunology
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.20110845

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.