1. IL-33 receptor ST2 regulates the cognitive impairments associated with experimental cerebral malaria
- Author
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Reverchon, Flora, Mortaud, Stéphane, Sivoyon, Maëliss, Maillet, Isabelle, Laugeray, Anthony, Palomo, Jennifer, Montécot, Céline, Herzine, Améziane, Meme, Sandra, Meme, William, Erard, François, Ryffel, Bernhard, Menuet, Arnaud, Quesniaux, Valérie F. J., Immunologie et Neurogénétique Expérimentales et Moléculaires (INEM), Centre National de la Recherche Scientifique (CNRS)-Université d'Orléans (UO), University of Geneva [Switzerland], Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), and Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
lcsh:Immunologic diseases. Allergy ,Central Nervous System ,Male ,Macroglial Cells ,Plasmodium berghei ,[SDV]Life Sciences [q-bio] ,Cognitive Neuroscience ,Interleukin-1beta ,Malaria, Cerebral ,Glial Cells ,Mouse Models ,Research and Analysis Methods ,Hippocampus ,Nervous System ,Mice ,Model Organisms ,Animal Cells ,parasitic diseases ,Medicine and Health Sciences ,Parasitic Diseases ,Animals ,Humans ,Cognitive Dysfunction ,lcsh:QH301-705.5 ,Microglial Cells ,ComputingMilieux_MISCELLANEOUS ,Cognitive Impairment ,Cognitive Neurology ,Biology and Life Sciences ,Brain ,Cell Biology ,Animal Models ,Tropical Diseases ,Interleukin-33 ,Interleukin-1 Receptor-Like 1 Protein ,Malaria ,Mice, Inbred C57BL ,lcsh:Biology (General) ,Neurology ,Experimental Organism Systems ,Astrocytes ,Cognitive Science ,Female ,Cerebral Malaria ,Cellular Types ,Anatomy ,lcsh:RC581-607 ,Research Article ,Neuroscience - Abstract
Cerebral malaria (CM) is associated with a high mortality rate and long-term neurocognitive impairment in survivors. The murine model of experimental cerebral malaria (ECM) induced by Plasmodium berghei ANKA (PbA)-infection reproduces several of these features. We reported recently increased levels of IL-33 protein in brain undergoing ECM and the involvement of IL-33/ST2 pathway in ECM development. Here we show that PbA-infection induced early short term and spatial memory defects, prior to blood brain barrier (BBB) disruption, in wild-type mice, while ST2-deficient mice did not develop cognitive defects. PbA-induced neuroinflammation was reduced in ST2-deficient mice with low Ifng, Tnfa, Il1b, Il6, CXCL9, CXCL10 and Cd8a expression, associated with an absence of neurogenesis defects in hippocampus. PbA-infection triggered a dramatic increase of IL-33 expression by oligodendrocytes, through ST2 pathway. In vitro, IL-33/ST2 pathway induced microglia expression of IL-1β which in turn stimulated IL-33 expression by oligodendrocytes. These results highlight the IL-33/ST2 pathway ability to orchestrate microglia and oligodendrocytes responses at an early stage of PbA-infection, with an amplification loop between IL-1β and IL-33, responsible for an exacerbated neuroinflammation context and associated neurological and cognitive defects., Author summary The cerebral complication of malaria caused by Plasmodium falciparum infection, is associated with long-term neurological sequelae in survivors. The mechanisms involved in neurocognitive impairments during cerebral malaria development are still unknown. We reported recently the essential role of IL-33/ST2 pathway in experimental cerebral malaria (ECM) development. In this study we investigated the capacity of IL-33, highly expressed in oligodendrocytes, to promote ECM-associated neurological and cognitive damages. We found that IL-33/ST2 pathway through glial cells is involved in neurocognitive impairments, associated with exacerbated neuroinflammation, and altered neurogenesis. Interestingly, the implication of glial cells with a high level of IL-33 production in neurocognitive disorders, occurs at an early stage of ECM development, prior to blood brain barrier permeabilization. We propose the link between microglial IL-1β and oligodendrocytes IL-33 production in neurological symptoms associated with ECM.
- Published
- 2017