Protection of Batf3-deficient mice from experimental cerebral malaria correlates with impaired cytotoxic T-cell responses and immune regulation.
Immunology
; 159(2): 193-204, 2020 02.
Article
em En
| MEDLINE
| ID: mdl-31631339
ABSTRACT
Excessive inflammatory immune responses during infections with Plasmodium parasites are responsible for severe complications such as cerebral malaria (CM) that can be studied experimentally in mice. Dendritic cells (DCs) activate cytotoxic CD8+ T-cells and initiate immune responses against the parasites. Batf3-/- mice lack a DC subset, which efficiently induces strong CD8 T-cell responses by cross-presentation of exogenous antigens. Here we show that Batf3-/- mice infected with Plasmodium berghei ANKA (PbA) were protected from experimental CM (ECM), characterized by a stable blood-brain barrier (BBB) and significantly less infiltrated peripheral immune cells in the brain. Importantly, the absence of ECM in Batf3-/- mice correlated with attenuated responses of cytotoxic T-cells, as their parasite-specific lytic activity as well as the production of interferon gamma and granzyme B were significantly decreased. Remarkably, spleens of ECM-protected Batf3-/- mice had elevated levels of regulatory immune cells and interleukin 10. Thus, protection from ECM in PbA-infected Batf3-/- mice was associated with the absence of strong CD8+ T-cell activity and induction of immunoregulatory mediators and cells.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Plasmodium berghei
/
Proteínas Repressoras
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Células Dendríticas
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Encéfalo
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Linfócitos T Citotóxicos
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Malária Cerebral
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Fatores de Transcrição de Zíper de Leucina Básica
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Immunology
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Alemanha