Crosstalk between Toll-like receptor 3 and Notch signaling contributes to CD14+ monocytes activity in enterovirus 71 infected hand, foot, and mouth disease.

Abstract

Interaction between Toll-like receptor (TLR) and Notch signaling contributes to inflammatory response in nephropathy and fungicidal infection, however, the role of this crosstalk remains not fully elucidated in enterovirus 71 (EV71)-induced hand, foot, and mouth disease (HFMD). The aim of this study was to investigate the crosstalk between TLR and Notch in inflammatory regulation in EV71 infection. Thirty-seven EV-71-indcued HFMD (16 mild and 21 severe cases) and eleven normal control (NC) were enrolled. CD14+ monocytes were purified, and were stimulated with either TLR3/4 agonists [poly(I: C) or LPS] or Notch signaling inhibitor. TLRs and Notch receptors expression, proinflammatory cytokines production, and important molecules in signaling pathways were measured by real-time PCR, ELISA, and Western blot. TLR3 and TLR4 was significantly elevated in CD14+ monocytes from HFMD patients than NC. Notch1 and Notch2 mRNA was also remarkably increased in CD14+ monocytes from severe HFMD. Poly(I: C) stimulation resulted in robust increase of IL-8, IL-6, and TNF-α by CD14+ monocytes in severe HFMD compared to NC. Activation of Notch1, Notch2, and target genes, Hes1 and Hes5 was also enhanced upon ploy(I: C) treatment. Although inhibition of Notch signaling did not affect TLR3 expression, poly(I: C)-induced inflammatory response was robustly attenuated, which was accompanied by silencing Src phosphorylation in CD14+ monocytes from severe HFMD patients. The current data indicated that crosstalk between TLR3 and Notch signaling modulated CD14+ monocytes function and inflammatory responses in the progression of EV71-induced HFMD.

• Authors: Jie Hao, Peiling Li, Yunjiao Tian, Yanhua Wang, Suqing Li, Lina Wang, Shujun Li
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 60 Pg. 26-33 (Jul 2018) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 29702280 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier B.V. All rights reserved.

Chemical References

• Cytokines
• Lipopolysaccharide Receptors
• NOTCH1 protein, human
• NOTCH2 protein, human
• Receptor, Notch1
• Receptor, Notch2
• TLR3 protein, human
• TLR4 protein, human
• Toll-Like Receptor 3
• Toll-Like Receptor 4
• Poly I-C

Topics

• Cells, Cultured
• Child, Preschool
• Cytokines (blood, metabolism)
• Enterovirus A, Human
• Female
• Hand, Foot and Mouth Disease (blood)
• Humans
• Lipopolysaccharide Receptors (metabolism)
• Male
• Monocytes (drug effects, metabolism)
• Poly I-C (pharmacology)
• Receptor, Notch1 (genetics)
• Receptor, Notch2 (genetics)
• Signal Transduction
• Toll-Like Receptor 3 (metabolism)
• Toll-Like Receptor 4 (metabolism)