Abstract
Viral myocarditis (VMC) caused by coxsackievirus B3 (CVB3) infection is a life-threatening disease. The cardiac damage during VMC is not mainly due to the direct cytotoxic effect of the virus on cardiomyocytes but mostly involves the induction of immune responses. Integrin CD11b plays an important role in immune response, for instance, in the induction of Th17 cells. However, the role of CD11b in the pathogenesis of VMC remains largely unknown. In the present study, a mouse model of VMC was established by CVB3 infection and CD11b was knocked down in the VMC mice by transfection with siRNA-CD11b. The expression of CD11b and IL-17 in heart tissues, frequency of Th17 cells in spleen tissues and serum IL-17 levels were measured using quantitative RT-PCR, Western blot, immunohistochemistry, flow cytometry and ELISA. Results showed that CVB3 infection caused the pathological changes in heart tissues with the increases in the following indexes: expression of CD11b and IL-17 in heart tissues, frequency of Th17 cells in spleen tissues and serum IL-17 levels. The expression of CD11b was positively correlated with IL-17 expression in heart tissues. Depletion of CD11b attenuated the damage caused by CVB3 and decreased the frequency of Th17 cells in spleen tissues as well as in IL-17, IL-23 and STAT3 expression in heart tissues. In summary, our findings reveal that disruption of CD11b function reduced CVB3-induced myocarditis, suggesting that CD11b may be a novel therapeutic target for VMC.
Highlights
Viral myocarditis (VMC), which is primarily induced by coxsackievirus B (CVB), is a life-threatening disease
Previous studies suggest that Th17 cell subsets and their effector IL-17 participate in the pathogenesis of VMC, because of the accumulation of Th17 cells throughout the course of VMC and the role of IL-17 in raising a variety of inflammatory factors, such as TNF-α, IL-1 and IL-6 [9–11]
In the myocardium of Coxsackievirus B3 (CVB3)-infected mice, there is an inflammatory reaction characterized by the infiltration and expression of inflammatory mediators of lymphoid and myeloid cells which are believed to be responsible for the pathogenesis of VMC [26]
Summary
Viral myocarditis (VMC), which is primarily induced by coxsackievirus B (CVB), is a life-threatening disease. Massive replication of CVB and other viruses in cardiomyocytes triggers the strong host immune response characterized by the infiltration of immune cells and secretion of inflammatory factors, which result in myocardial damage [1,2]. CVB3 infection results in irreversible cytopathic effects at the cellular level and cardiac damage at the tissue level [4,6]. Studies have shown that Th17 cells mediate the tissue damage of a variety of autoimmune diseases [7,8]. Previous studies suggest that Th17 cell subsets and their effector IL-17 participate in the pathogenesis of VMC, because of the accumulation of Th17 cells throughout the course of VMC and the role of IL-17 in raising a variety of inflammatory factors, such as TNF-α, IL-1 and IL-6 [9–11]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call