%0 Journal Article
%T IL-33 receptor ST2 regulates the cognitive impairments associated with experimental cerebral malaria
%A Am¨¦ziane Herzine
%A Anthony Laugeray
%A Arnaud Menuet
%A Bernhard Ryffel
%A C¨¦line Mont¨¦cot
%A Flora Reverchon
%A Fran£¿ois Erard
%A Isabelle Maillet
%A Jennifer Palomo
%A Ma£¿liss Sivoyon
%A Sandra Meme
%A St¨¦phane Mortaud
%A Val¨¦rie F. J. Quesniaux
%A William Meme
%J -
%D 2017
%R 10.1371/journal.ppat.1006322
%X 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-1¦Â 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-1¦Â and IL-33, responsible for an exacerbated neuroinflammation context and associated neurological and cognitive defects
%K Cerebral malaria
%K Cognitive impairment
%K Microglial cells
%K Hippocampus
%K Mouse models
%K Cognitive neurology
%K Central nervous system
%K Astrocytes
%U https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006322