| First Author | Reverchon F | Year | 2017 |
| Journal | PLoS Pathog | Volume | 13 |
| Issue | 4 | Pages | e1006322 |
| PubMed ID | 28448579 | Mgi Jnum | J:246921 |
| Mgi Id | MGI:5919873 | Doi | 10.1371/journal.ppat.1006322 |
| Citation | Reverchon F, et al. (2017) IL-33 receptor ST2 regulates the cognitive impairments associated with experimental cerebral malaria. PLoS Pathog 13(4):e1006322 |
| abstractText | 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-1beta 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-1beta and IL-33, responsible for an exacerbated neuroinflammation context and associated neurological and cognitive defects. |
