Th17 Cells Contribute to Viral Replication in Coxsackievirus B3-Induced Acute Viral Myocarditis

Abstract

Acute viral myocarditis (AVMC) is characterized by virus-triggered myocardial inflammation, and Coxsackievirus B3 (CVB3) is the primary pathogen. We previously proved that Th17 cells, besides having proinflammatory effects, were involved in AVMC by enhancing humoral response. However, the relationship between Th17 cells and CVB3 replication remains unknown. In this experiment, we infected BALB/c mice with CVB3 for establishing AVMC models and then found that, with the increase of viral replication, the expressions of splenic Th17 cells, serum IL-17, and cardiac IL-17 mRNA were elevated significantly, accompanied by the progressive cardiac injuries of AVMC. Furthermore, on day 5, the peak time for viral replication, correlation was positive between cardiac IL-17 mRNA and CVB3 RNA (correlation index = 0.835; p < 0.01). Although the expressions of Th1 and CD8+ T cells, which could secrete the antiviral cytokine IFN-γ and damage the heart, were also elevated, along with Th17 cells, in AVMC, the neutralization of IL-17 further upregulated the percentages of splenic Th1 and CD8+ T cells and the levels of cardiac IFN-γ mRNA. The cardiac pathological changes were obviously improved after neutralization, with reduced viral replication followed by decreases in the cardiac inflammatory cytokines IL-17, TNF-α, and IL-1β. These data suggest that Th17 cells contribute to CVB3 replication in AVMC, and that IL-17 might be an important target for regulating the balance of antiviral immunities.

Possible pathogenic role of T helper type 9 cells and interleukin (IL)-9 in atopic dermatitis

“…Interleukin (IL)-17-expressing T cells (termed Th17) and forkhead box protein 3 (FoxP3 + ) regulatory T cells (Treg) are newly identified subsets of CD4 + Th cells, and developing studies have reported that both of them have a pathogenic role in AD [3][4][5]. More recently, a novel independent Th-cell subset, characterized by expression of high amounts of IL-9, which do not express T-bet, GATA-3, retinoic acidrelated orphan receptor gamma T (RORγt) or FoxP3, subset-determining transcription factors associated with Th1, Th2, Th17 and Treg cells, had been recognized as 'Th9' cells [6][7][8][9]. Although the mechanism for the differentiation and proliferation of Th9 cells has not been elucidated fully, the transcription factor PU.1 is required for the differentiation and functional activation of Th9 cells; indeed, PU.1 binds directly to the IL-9 promoter to trigger specific chromatin modifications [10][11][12].…”

Advances in monoclonal antibody application in myocarditis

“…Studies show that in VMC mice, myocardial histological changes are similar to anthropology lymphocytic myocarditis (Yuan et al, 2010b), and thus this model has been widely used for studying both the acute infectious phase and the chronic immune phase of human VMC. Both the direct viral response and immune-mediated mechanisms have been shown to contribute to the pathogenesis of acute injury and subsequent cardiac remodeling (McManus et al, 1993;Cooper, 2003).…”

The Key Players of Coxsackievirus-Induced Myocarditis

“…Cardiac pathology was improved after IL-17 neutralization and correlated with reduced viral replication and decreases in cardiac inflammatory cytokines IL-17, TNF-, and IL-1 . This study implicates Th17 cells in contributing coxsackeivirus B3 replication in viral myocarditis, and implicates IL-17 as a target for regulating antiviral immune responses (Yuan et al 2010). Th17 cells are activated by IL-23, a cytokine likely produced by activated macrophages and dendritic cells, through receptor interactions made of IL-12R 1 and IL-23 receptor (Langrish et al 2005).…”