Absence of IL-20 receptor 1 reduced the lethality of enterovirus 71-infected mice

Abstract

Enterovirus 71 (EV71) has induced fatal encephalitis in thousands of young children in the Asia-Pacific region since the past decade Cytokines are elevated in infected patients with brainstem encephalitis Mouse studies show that cytokines can regulate the severity of EV71-induced disease Cytokines IL-19 and IL-20 are shown to be associated with overwhelming inflammatory diseases such as psoriasis and rheumatoid arthritis Few studies have investigated the induction and importance of these cytokines in EV71 infection We first determined IL-19 and IL-20 levels in EV71-infected mice and found that EV71 infection significantly enhanced the levels of IL-19 but not IL-20 in the mouse brain and serum IL-19 was expressed in the brain neuron IL-19 is the ligand of type I IL-20 receptor complex that is comprised of IL-20R1 and IL-20R2 We examined and found that EV71 infection significantly increased the mouse brain level of IL-20R1 which was expressed in the brain neuron Moreover we found that after EV71 infection the survival rate of IL-20R1 knockout mice was significantly higher than that of wild-type mice by 46% In addition the mean viral titers in the central nervous system of IL-20R1 knockout mice were significantly lower than those of wild-type mice Furthermore we found that absence of IL-20R1 affected cytokine expression with decreases in the brain IL-1β levels of both mock-infected and infected mice Our findings also showed that IL-20R1 deficiency significantly decreased CD19+ B cells in the infected mouse spleen and CD4+ cells in the infected mouse brain These results collectively show that type I IL-20 receptor affects the disease progression of EV71-infected mice

Date of Award	2014 Jul 25
Original language	English
Supervisor	Shun-hua Chen (Supervisor)