Type I interferons contribute to experimental cerebral malaria development in response to sporozoite or blood-stage Plasmodium berghei ANKA.
Eur J Immunol
; 43(10): 2683-95, 2013 Oct.
Article
en En
| MEDLINE
| ID: mdl-23780878
ABSTRACT
Cerebral malaria is a severe complication of Plasmodium falciparum infection. Although T-cell activation and type II IFN-γ are required for Plasmodium berghei ANKA (PbA)-induced murine experimental cerebral malaria (ECM), the role of type I IFN-α/ß in ECM development remains unclear. Here, we address the role of the IFN-α/ß pathway in ECM devel-opment in response to hepatic or blood-stage PbA infection, using mice deficient for types I or II IFN receptors. While IFN-γR1â»/â» mice were fully resistant, IFNAR1â»/â» mice showed delayed and partial protection to ECM after PbA infection. ECM resistance in IFN-γR1â»/â» mice correlated with unaltered cerebral microcirculation and absence of ischemia, while WT and IFNAR1â»/â» mice developed distinct microvascular pathologies. ECM resistance appeared to be independent of parasitemia. Instead, key mediators of ECM were attenuated in the absence of IFNAR1, including PbA-induced brain sequestration of CXCR3âº-activated CD8⺠T cells. This was associated with reduced expression of Granzyme B, IFN-γ, IL-12Rß2, and T-cell-attracting chemokines CXCL9 and CXCL10 in IFNAR1â»/â» mice, more so in the absence of IFN-γR1. Therefore, the type I IFN-α/ß receptor pathway contributes to brain T-cell responses and microvascular pathology, although it is not as essential as IFN-γ for the development of cerebral malaria upon hepatic or blood-stage PbA infection.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Plasmodium berghei
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Plasmodium falciparum
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Interferón Tipo I
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Cerebelo
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Malaria Cerebral
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Linfocitos T CD8-positivos
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Eur J Immunol
Año:
2013
Tipo del documento:
Article
País de afiliación:
Francia