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Article Open Access

The immune mechanism of intestinal tract Toll-like receptor in mediating EV71 virus type severe hand-foot-and-mouth disease and the MAPK pathway

  • Authors:
    • Lei Zhu
    • Weihua Li
    • Gongjian Qi
    • Na Liu
    • Liping Sheng
    • Lei Shang
    • Boxiang Qi
  • View Affiliations / Copyright

    Affiliations: Department of Intensive Care Unit, Xuzhou Children's Hospital, Xuzhou, Jiangsu 221006, P.R. China
    Copyright: © Zhu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2263-2266
    |
    Published online on: March 20, 2017
       https://doi.org/10.3892/etm.2017.4245
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Abstract

Immunological response is thought to play a crucial role in the development of a severe hand-foot-and-mouth disease (HFMD) infection in children, but the mechanisms remain largely unknown. This study was designed to help in elucidating the immunopathological pathways involved in the disease by quantifying Toll-like receptor (TLR) mRNAs, MAPK factors and cytokine levels in children experiencing the disease. A total of 86 enterovirus 71 (EV71)‑infected HFMD children (49 with mild and 27 with severe disease), along with 30 healthy children were involved in the study. Peripheral vein blood samples were collected from each individual, and used to isolate peripheral blood mononuclear cells (PBMCs) for mRNA extraction and sera for measuring levels of tumor necrosis factor (TNF)‑α, interferon (IFN)‑γ, interleukin (IL)‑6 and IL‑10. The average expression levels of TLR3, TLR4, TLR7 and TLR8 mRNA in PBMCs of children with severe HFMD were significantly higher than those in the other children, the lowest values were found in the healthy control group (P<0.05). The expression levels of TLR2 and TLR9 mRNA were not significantly different (P>0.05) among the groups. Additionally, the expression levels of TNF‑α, IFN‑γ, IL‑6 and IL‑10 in the serum of the children in the severe group were significantly higher than those in the other two groups, and the lowest values were again found in the control group (P<0.05). Pearson correlation analysis showed that the TLR3, TLR4, TLR7 and TLR8 mRNA levels in PBMCs were positively correlated with the TNF-α, IFN-γ, IL‑6 and IL‑10 levels in the serum (P<0.05). Furthermore, the expression levels of the ERK, JNK and p38 mRNA in PBMCs of children in the severe group were significantly higher than those in the other two groups, with the lowest values being in the control group (P<0.05). Pearson correlation analysis showed that the TLR3, TLR4, TLR7 and TLR8 mRNA levels in PBMCs were positively correlated with ERK, JNK and p38 mRNA levels (P<0.05). The results of our study seem to indicate that the high expression levels of TLR3, TLR4, TLR7 and TLR8 induced in severe EV71 HFMD regulate the expression of cytokines by MAPK signaling pathway and negatively affect the ability of the organism to resolve the infection. Further studies are needed to test the hypothesis that immuno-modulation would be an effective treatment approach in pediatric cases of severe HFMD.
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Copy and paste a formatted citation
Spandidos Publications style
Zhu L, Li W, Qi G, Liu N, Sheng L, Shang L and Qi B: The immune mechanism of intestinal tract Toll-like receptor in mediating EV71 virus type severe hand-foot-and-mouth disease and the MAPK pathway. Exp Ther Med 13: 2263-2266, 2017.
APA
Zhu, L., Li, W., Qi, G., Liu, N., Sheng, L., Shang, L., & Qi, B. (2017). The immune mechanism of intestinal tract Toll-like receptor in mediating EV71 virus type severe hand-foot-and-mouth disease and the MAPK pathway. Experimental and Therapeutic Medicine, 13, 2263-2266. https://doi.org/10.3892/etm.2017.4245
MLA
Zhu, L., Li, W., Qi, G., Liu, N., Sheng, L., Shang, L., Qi, B."The immune mechanism of intestinal tract Toll-like receptor in mediating EV71 virus type severe hand-foot-and-mouth disease and the MAPK pathway". Experimental and Therapeutic Medicine 13.5 (2017): 2263-2266.
Chicago
Zhu, L., Li, W., Qi, G., Liu, N., Sheng, L., Shang, L., Qi, B."The immune mechanism of intestinal tract Toll-like receptor in mediating EV71 virus type severe hand-foot-and-mouth disease and the MAPK pathway". Experimental and Therapeutic Medicine 13, no. 5 (2017): 2263-2266. https://doi.org/10.3892/etm.2017.4245
Copy and paste a formatted citation
x
Spandidos Publications style
Zhu L, Li W, Qi G, Liu N, Sheng L, Shang L and Qi B: The immune mechanism of intestinal tract Toll-like receptor in mediating EV71 virus type severe hand-foot-and-mouth disease and the MAPK pathway. Exp Ther Med 13: 2263-2266, 2017.
APA
Zhu, L., Li, W., Qi, G., Liu, N., Sheng, L., Shang, L., & Qi, B. (2017). The immune mechanism of intestinal tract Toll-like receptor in mediating EV71 virus type severe hand-foot-and-mouth disease and the MAPK pathway. Experimental and Therapeutic Medicine, 13, 2263-2266. https://doi.org/10.3892/etm.2017.4245
MLA
Zhu, L., Li, W., Qi, G., Liu, N., Sheng, L., Shang, L., Qi, B."The immune mechanism of intestinal tract Toll-like receptor in mediating EV71 virus type severe hand-foot-and-mouth disease and the MAPK pathway". Experimental and Therapeutic Medicine 13.5 (2017): 2263-2266.
Chicago
Zhu, L., Li, W., Qi, G., Liu, N., Sheng, L., Shang, L., Qi, B."The immune mechanism of intestinal tract Toll-like receptor in mediating EV71 virus type severe hand-foot-and-mouth disease and the MAPK pathway". Experimental and Therapeutic Medicine 13, no. 5 (2017): 2263-2266. https://doi.org/10.3892/etm.2017.4245
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