Key result
Severe EV71 hand-foot-and-mouth disease was associated with significantly higher expression levels of TLR3, TLR4, TLR7, and TLR8 mRNAs in PBMCs compared to mild disease and healthy controls (P<0.05).
Observational (n=116)
No
Severe EV71 hand-foot-and-mouth disease is associated with upregulated TLR3, TLR4, TLR7, and TLR8 expression, which correlates with increased inflammatory cytokines and MAPK signaling pathway activation.
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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Zhu et al. (2017) conducted an observational in Hand-foot-and-mouth disease (HFMD) caused by EV71 (n=116). Severe EV71 HFMD infection vs. Mild EV71 HFMD and healthy controls was evaluated on Expression levels of TLR3, TLR4, TLR7 and TLR8 mRNA in PBMCs (p=<0.05). Severe EV71 hand-foot-and-mouth disease was associated with significantly higher expression levels of TLR3, TLR4, TLR7, and TLR8 mRNAs in PBMCs compared to mild disease and healthy controls (P<0.05).
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