Abstract
BackgroundHand, foot and mouth disease (HFMD), a virus-induced infectious disease that usually affects infants and children, has an increased incidence in China in recent years. This study attempted to investigate the role of the Notch signaling pathway in the pathogenesis of HFMD.MethodsEighty-two children diagnosed with HFMD were enrolled into this study. The HFMD group was further divided into the uncomplicated HFMD and HFMD with encephalitis groups. The control group included 40 children who underwent elective surgery for treatment of inguinal hernias.ResultsChildren with HFMD displayed significantly reduced CD3+, CD3+CD4+ and CD3+CD8+ cell subsets, but substantially enhanced CD3−CD19+ cell subset (p < 0.05 versus control subjects). The expression levels of Notch ligands Dll1 and Dll4 in the peripheral blood of the HFMD group were significantly higher than those in the control group (p < 0.05). There were statistically significant differences in CD3+, CD3+CD4+ and CD3−CD19+ cell subsets, but not in Notch ligand expression, between the uncomplicated HFMD and HFMD with encephalitis groups. Dll4 expression in HFMD subjects correlated negatively with the CD3+ and CD3+CD8+ cell subsets (p < 0.05), but positively with the CD3−CD19+ cell subset (p < 0.05). Furthermore, Dll4 expression in HFMD with encephalitis subjects correlated positively with total white blood cell (WBC) counts and total protein contents in cerebrospinal fluid (CSF) (p < 0.05).ConclusionsThe Notch ligand Dll4 exhibits a strong correlation with the CD3+, CD3+CD8+ and CD3−CD19+ cell subsets in children with HFMD, indicating that the Notch signaling may be involved in the development of HFMD by affecting the number and status of peripheral lymphocytes.
Highlights
Hand, foot and mouth disease (HFMD), a virus-induced infectious disease that usually affects infants and children, has an increased incidence in China in recent years
The numbers of peripheral CD3+ (p = 0.023) and CD3+CD4+ (p = 0.039) cells in the uncomplicated HFMD group were substantially higher than those in the HFMD with encephalitis group, whereas the number of peripheral CD3−CD19+ cells (p = 0.001) was significantly lower in the uncomplicated HFMD group compared to the HFMD with encephalitis group (Table 2)
We found significant increases in the expression levels of Notch ligands Dll1 and Dll4 in the peripheral blood of children with HFMD, suggesting that Notch signaling might be initiated and activated during HFMD via the engagement of upregulated Notch ligand Dll1 or Dll4 with
Summary
Foot and mouth disease (HFMD), a virus-induced infectious disease that usually affects infants and children, has an increased incidence in China in recent years. This study attempted to investigate the role of the Notch signaling pathway in the pathogenesis of HFMD. Foot and mouth disease (HFMD) is a common infectious disease worldwide, which usually affects infants and children. HFMD has become increasingly prevalent in the Asia-pacific region, in China. HFMD is contagious and can be lethal in infants and children with severe cases. The major pathogens of HFMD in these cases were enterovirus 71 (EV71) and coxsackie A virus A16 (CoxA 16) [1,2], but the precise mechanism (s) for the pathogenesis of HFMD has not yet been fully elucidated. Previous studies reported that children with HFMD displayed substantial immune disorders [3,4]
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