1. Critical role of the neutrophil-associated high-affinity receptor for IgE in the pathogenesis of experimental cerebral malaria.
- Author
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Porcherie A, Mathieu C, Peronet R, Schneider E, Claver J, Commere PH, Kiefer-Biasizzo H, Karasuyama H, Milon G, Dy M, Kinet JP, Louis J, Blank U, and Mécheri S
- Subjects
- Adoptive Transfer, Animals, Basophils cytology, Basophils immunology, Cytokines immunology, Eosinophils cytology, Eosinophils immunology, Female, Immunoglobulin E genetics, Malaria, Cerebral parasitology, Mice, Mice, Inbred C57BL, Mice, Knockout, Neutrophils cytology, Plasmodium berghei immunology, Plasmodium berghei pathogenicity, Protein Isoforms genetics, Protein Isoforms immunology, Receptors, IgE genetics, Immunoglobulin E immunology, Malaria, Cerebral immunology, Malaria, Cerebral pathology, Neutrophils immunology, Receptors, IgE immunology
- 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.
- Published
- 2011
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