IL-33 receptor ST2 regulates the cognitive impairments associated with experimental cerebral malaria.
PLoS Pathog
; 13(4): e1006322, 2017 Apr.
Article
in En
| MEDLINE
| ID: mdl-28448579
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-1ß 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-1ß and IL-33, responsible for an exacerbated neuroinflammation context and associated neurological and cognitive defects.
Full text:
1
Database:
MEDLINE
Main subject:
Plasmodium berghei
/
Brain
/
Malaria, Cerebral
/
Cognitive Dysfunction
/
Interleukin-33
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Interleukin-1 Receptor-Like 1 Protein
Type of study:
Etiology_studies
/
Risk_factors_studies
Limits:
Animals
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Female
/
Humans
/
Male
Language:
En
Year:
2017
Type:
Article