Critical role of the neutrophil-associated high affinity receptor for IgE in the pathogenesis of experimental cerebral malaria
Résumé
The role of the IgE-Fc epsilon RI complex in malaria severity in Plasmodium falciparum-hosting patients is unknown. We demonstrate that mice genetically deficient for the high-affinity receptor for IgE (Fc epsilon RI alpha-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 Fc epsilon RI+ neutrophil population, which is not observed in mice hosting a non-ECM-inducing PbNK65 parasite strain. Depletion of this Fc epsilon RI+ neutrophil population prevents ECM, whereas transfer of this population into Fc epsilon RI alpha -KO mice restores ECM susceptibility. Fc epsilon RI+ 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 Fc epsilon RI-expressing neutrophil subpopulation in malaria disease severity.
Domaines
Immunologie| Origine | Publication financée par une institution |
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