Immunomodulatory cytokines determine the outcome of Japanese encephalitis virus infection in mice.
Japanese encephalitis virus (JEV) induces an acute infection of the central nervous system, the pathogenic mechanism of which is not fully understood. To investigate host response to JEV infection, 14-day-old mice were infected via the extraneural route, which resulted in encephalitis and death. Mice that received JEV immune splenocyte transfer were protected from extraneural JEV infection. Pathology and gene expression profiles were then compared in brains of mice that either succumbed to JEV infection or were protected from infection by JEV immune cell transfer. Mice undergoing progressive JEV infection had increased expression of proinflammatory cytokines, chemokines, and signal transducers associated with the interferon (IFN) pathway. In contrast, mice receiving immune cell transfer had increased production of the Th2 cytokine IL-4, and of IL-10, with subdued expression of IFN-gamma. We observed IL-10 to be an important factor in determining clinical outcome in JEV infection. Data obtained by microarray analysis were further confirmed by quantitative RT-PCR. Together, these data suggest that JEV infection causes an unregulated inflammatory response that can be countered by the expression of immunomodulatory cytokines in mice that survive lethal infection.
Biswas
S M
SM
National Institute of Virology, Sus Road Campus, Pashan, Pune, Maharashtra, India.
Kar
S
S
Singh
R
R
Chakraborty
D
D
Vipat
V
V
Raut
C G
CG
Mishra
A C
AC
Gore
M M
MM
Ghosh
D
D
D019264:Adoptive Transfer; D000818:Animals; D001921:Brain / Q000473:pathology / Q000821:virology; D016207:Cytokines / Q000276:immunology* / Q000633:toxicity*; D004195:Disease Models, Animal; D004664:Encephalitis Virus, Japanese / Q000276:immunology*; D004672:Encephalitis, Japanese / Q000276:immunology* / Q000473:pathology*; D020869:Gene Expression Profiling; D006801:Humans; D007249:Inflammation / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016207:Cytokines