Sporozoite-mediated hepatocyte wounding limits Plasmodium parasite development via MyD88-mediated NF-kappa B activation and inducible NO synthase expression

Détails

ID Serval
serval:BIB_E1DD33F82039
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Sporozoite-mediated hepatocyte wounding limits Plasmodium parasite development via MyD88-mediated NF-kappa B activation and inducible NO synthase expression
Périodique
Journal of Immunology
Auteur(s)
Torgler R., Bongfen S. E., Romero J. C., Tardivel A., Thome M., Corradin G.
ISSN
0022-1767
Statut éditorial
Publié
Date de publication
2008
Peer-reviewed
Oui
Volume
180
Numéro
6
Pages
3990-3999
Langue
anglais
Résumé
Plasmodium sporozoites traverse several host cells before infecting hepatocytes. In the process, the plasma membranes of the cells are ruptured, resulting in the release of cytosolic factors into the microenvironment. This released endogenous material is highly stimulatory/immunogenic and can serve as a danger signal initiating distinct responses in various cells. Thus, our study aimed at characterizing the effect of cell material leakage during Plasmodium infection on cultured mouse primary hepatocytes and HepG2 cells. We observed that wounded cell-derived cytosolic factors activate NF-kappaB, a main regulator of host inflammatory responses, in cells bordering wounded cells, which are potential host cells for final parasite infection. This activation of NF-kappaB occurred shortly after infection and led to a reduction of infection load in a time-dependent manner in vitro and in vivo, an effect that could be reverted by addition of the specific NF-kappaB inhibitor BAY11-7082. Furthermore, no NF-kappaB activation was observed when Spect(-/-) parasites, which are devoid of hepatocyte traversing properties, were used. We provide further evidence that NF-kappaB activation causes the induction of inducible NO synthase expression in hepatocytes, and this is, in turn, responsible for a decrease in Plasmodium-infected hepatocytes. Furthermore, primary hepatocytes from MyD88(-/-) mice showed no NF-kappaB activation and inducible NO synthase expression upon infection, suggesting a role of the Toll/IL-1 receptor family members in sensing cytosolic factors. Indeed, lack of MyD88 significantly increased infection in vitro and in vivo. Thus, host cell wounding due to parasite migration induces inflammation which limits the extent of parasite infection
Mots-clé
Animals , Biochemistry , biosynthesis , Cell Line,Tumor , Cells,Cultured , Cytosol , deficiency , enzymology , Gene Expression Regulation,Developmental , genetics , growth & development , Hepatocytes , immunology , Infection , Inflammation , Malaria , metabolism , Mice , Mice,Inbred C57BL , Mice,Knockout , Myeloid Differentiation Factor 88 , NF-kappa B , Nitric Oxide , Nitric Oxide Synthase , Nitric Oxide Synthase Type II , parasitology , pathology , physiology , Plasma , Plasmodium berghei , prevention & control , secretion , Sporozoites , Switzerland , Wound Healing
Pubmed
Web of science
Création de la notice
29/01/2009 22:13
Dernière modification de la notice
20/08/2019 16:05
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