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Critical role of the neutrophil-associated high-affinity receptor for IgE in the pathogenesis of experimental cerebral malaria.
- Source :
-
The Journal of experimental medicine [J Exp Med] 2011 Oct 24; Vol. 208 (11), pp. 2225-36. Date of Electronic Publication: 2011 Oct 03. - Publication Year :
- 2011
-
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.
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 1540-9538
- Volume :
- 208
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- The Journal of experimental medicine
- Publication Type :
- Academic Journal
- Accession number :
- 21967768
- Full Text :
- https://doi.org/10.1084/jem.20110845