Critical role of IL-33 receptor ST2 in experimental cerebral malaria development.
Eur J Immunol
; 45(5): 1354-65, 2015 May.
Article
en En
| MEDLINE
| ID: mdl-25682948
ABSTRACT
Cerebral malaria, a severe complication of Plasmodium falciparum infection, can be modeled in murine Plasmodium berghei ANKA (PbA) infection. PbA-induced experimental cerebral malaria (ECM) is CD8(+) T-cell mediated, and influenced by TH 1/TH 2 balance. Here, we show that IL-33 expression is increased in brain undergoing ECM and we address the role of the IL-33/ST2 pathway in ECM development. ST2-deficient mice were resistant to PbA-induced neuropathology. They survived >20 days with no ECM neurological sign and a preserved cerebral microcirculation, while WT mice succumbed within 10 days with ECM, brain vascular leakage, distinct microvascular pathology obstruction, and hemorrhages. Parasitemia and brain parasite load were similar in ST2-deficient and WT mice. Protection was accompanied by reduced brain sequestration of activated CD4(+) T cells and perforin(+) CD8(+) T cells. While IFN-γ and T-cell-attracting chemokines CXCL9 and CXCL10 were not affected in the absence of functional ST2 pathway, the local expression of ICAM-1, CXCR3, and LT-α, crucial for ECM development, was strongly reduced, and this may explain the diminished pathogenic T-cell recruitment and resistance to ECM. Therefore, IL-33 is induced in PbA sporozoite infection, and the pathogenic T-cell responses with local microvascular pathology are dependent on IL-33/ST2 signaling, identifying IL-33 as a new actor in ECM development.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Plasmodium berghei
/
Malaria Cerebral
/
Receptores de Interleucina
Tipo de estudio:
Etiology_studies
Límite:
Animals
Idioma:
En
Revista:
Eur J Immunol
Año:
2015
Tipo del documento:
Article
País de afiliación:
Francia
Pais de publicación:
ALEMANHA
/
ALEMANIA
/
DE
/
DEUSTCHLAND
/
GERMANY