The Effect Of Listeria Monocytogenes On Host Antiviral Immunity Response

L. monocytogenes is a facultative intracellular pathogen responsible for human listeriosis, a severe food-borne disease affects primarily pregnant women, newborns, adults with weakened immune systems, and the elderly. L. monocytogenes has emerged as a model for the study of host–pathogen interactions for many years. Recently, L. monocytogenes infection has been shown to directly target the host cell SUMOylation machinery. L. monocytogenes interferes with host cell SUMOylation by action of LLO, which causes degradation of the only SUMO-conjugating enzyme present in mammals, Ubc9. Co-infection, as a more real infetion with human infection, has becaome a hot spot in immunity research. Melanoma differentiation-associated gene 5 (MDA5) is a cytosolic viral RNA sensor that induce type I interferon production (IFN). Our laboratory results show that enhanced SUMOylation of MDA5 by exogenously expressed SUMO-conjugating enzyme Ubc9 correlated with up-regulation of IFN expression and repressed virus replication. In this work, we have demonstrated that L. monocytogenes decreased SUMOylation of MDA5.But to our surprise,we found that L. monocytogenes can decrease MDA5 protein level directly. We have further shown that LLO mediated the effect. Moreover, LLO decrease MDA5 level mightly not at the transecriptional level or transelational level, but at post-transcriptional level in a proteosome dependent manner. This was correlated with down-regulated MDA-5 driven IFN-βinduction and enhancing of virus replication.