Abstract
Myocardial injuries in viral myocarditis (VMC) are caused by viral infection and related autoimmune disorders. Recent studies suggest that IL-9 mediated both antimicrobial immune and autoimmune responses in addition to allergic diseases. However, the role of IL-9 in viral infection and VMC remains controversial and uncertain. In this study, we infected Balb/c mice with Coxsackievirus B3 (CVB3), and found that IL-9 was enriched in the blood and hearts of VMC mice on days 5 and 7 after virus infection. Most of IL-9 was secreted by CD8+ T cells on day 5 and CD4+ T cells on day 7 in the myocardium. Further, IL-9 knockout exacerbated cardiac damage following CVB3 infection, along with a sharp increase in viral replication and IL-17a expression, as well as a decrease in TGF-β. In contrast, the repletion of IL-9 in Balb/c mice with CVB infection induced the opposite effect. Studies in vitro further revealed that IL-9 directly inhibited viral replication in cardiomyocytes by reducing coxsackie and adenovirus receptor expression, which might be associated with upregulation of TGF-β autocrine effect in these cells. However, IL-9 had no direct effect on apoptosis in cardiomyocytes. Our data indicated that IL-9 played a protective role in disease progression by inhibiting CVB3 replication in the early stages of VMC.
Highlights
Viral myocarditis (VMC) is a triphasic disease including an initial viral infection, followed by autoimmune response and myocardial remodeling [1]
To identify the leukocytes contributing to cardiac IL-9 secretion in viral myocarditis (VMC), we stained the cells with various surface markers
Most of the IL-9-secreting leukocytes were CD8+ on day 5 and CD4+ on day 7 in the myocardium, suggesting that CD8+ and CD4+ T cells might be the major source of IL-9 in VMC
Summary
Viral myocarditis (VMC) is a triphasic disease including an initial viral infection, followed by autoimmune response and myocardial remodeling [1]. Coxsackievirus B3 (CVB3) is the common pathogen causing this inflammatory disease [2]. Excessive activation of immune response triggered by virus infection is the main factor contributing to myocardial injuries, the virus itself is critical to the progression of VMC via direct attack on cardiomyocytes [3]. The effect of IL-9 on VMC progression and CVB3 replication remain unknown. In this study, we investigated the expression of IL-9, viral replication, and related inflammatory factors in VMC using IL-9 knockout (IL-9KO/IL-9 −/−) and rIL-9 injected Balb/c mice. The direct effects of IL-9 Inhibits CVB3 Replication in AVMC
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