Intracranial Injection of Dengue Virus Induces Interferon Stimulated Genes and CD8 T Cell Infiltration by Sphingosine Kinase 1 Independent PathwaysReportar como inadecuado




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We have previously reported that the absence of sphingosine kinase 1 SK1 affects both dengue virus DENV infection and innate immune responses in vitro. Here we aimed to define SK1-dependancy of DENV-induced disease and the associated innate responses in vivo. The lack of a reliable mouse model with a fully competent interferon response for DENV infection is a challenge, and here we use an experimental model of DENV infection in the brain of immunocompetent mice. Intracranial injection of DENV-2 into C57BL-6 mice induced body weight loss and neurological symptoms which was associated with a high level of DENV RNA in the brain. Body weight loss and DENV RNA level tended to be greater in SK1- compared with wildtype WT mice. Brain infection with DENV-2 is associated with the induction of interferon-β IFN-β and IFN-stimulated gene ISG expression including viperin, Ifi27l2a, IRF7, and CXCL10 without any significant differences between WT and SK1- mice. The SK2 and sphingosine-1-phosphate S1P levels in the brain were unchanged by DENV infection or the lack of SK1. Histological analysis demonstrated the presence of a cellular infiltrate in DENV-infected brain with a significant increase in mRNA for CD8 but not CD4 suggesting this infiltrate is likely CD8+ but not CD4+ T-lymphocytes. This increase in T-cell infiltration was not affected by the lack of SK1. Overall, DENV-infection in the brain induces IFN and T-cell responses but does not influence the SK-S1P axis. In contrast to our observations in vitro, SK1 has no major influence on these responses following DENV-infection in the mouse brain.



Autor: Wisam H. Al-Shujairi , Jennifer N. Clarke, Lorena T. Davies, Mohammed Alsharifi, Stuart M. Pitson, Jillian M. Carr

Fuente: http://plos.srce.hr/



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