Hepatic Inflammation Confers Protective Immunity Against Liver Stages of Malaria Parasite.
Front Immunol
; 11: 585502, 2020.
Article
em En
| MEDLINE
| ID: mdl-33329563
Deciphering the mechanisms by which Plasmodium parasites develop inside hepatocytes is an important step toward the understanding of malaria pathogenesis. We propose that the nature and the magnitude of the inflammatory response in the liver are key for the establishment of the infection. Here, we used mice deficient in the multidrug resistance-2 gene (Mdr2-/-)-encoded phospholipid flippase leading to the development of liver inflammation. Infection of Mdr2-/- mice with Plasmodium berghei ANKA (PbANKA) sporozoites (SPZ) resulted in the blockade of hepatic exo-erythrocytic forms (EEFs) with no further development into blood stage parasites. Interestingly, cultured primary hepatocytes from mutant and wild-type mice are equally effective in supporting EEF development. The abortive infection resulted in a long-lasting immunity in Mdr2-/- mice against infectious SPZ where neutrophils and IL-6 appear as key effector components along with CD8+ and CD4+ effector and central memory T cells. Inflammation-induced breakdown of liver tolerance promotes anti-parasite immunity and provides new approaches for the design of effective vaccines against malaria disease.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Hepatócitos
/
Hepatite
/
Malária
Limite:
Animals
Idioma:
En
Revista:
Front Immunol
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
França
País de publicação:
Suíça