Expression and clinical significance of pattern recognition receptor-associated genes in hand, foot and mouth disease

Muqi Wang , Huiling Deng , Yuan Chen , Yikai Wang , Yufeng Zhang , Chenrui Liu , Meng Zhang , Ting Li , Shuangsuo Dang , Yaping Li

Asian Pacific Journal of Tropical Medicine ›› 2024, Vol. 17 ›› Issue (4) : 173 -183.

PDF (2306KB)
Asian Pacific Journal of Tropical Medicine ›› 2024, Vol. 17 ›› Issue (4) :173 -183. DOI: 10.4103/apjtm.apjtm_876_23
Original Article
research-article
Expression and clinical significance of pattern recognition receptor-associated genes in hand, foot and mouth disease
Author information +
History +
PDF (2306KB)

Abstract

Objective: To explore which pattern recognition receptors (PRRs) play a key role in the development of hand, foot, and mouth disease (HFMD) by analyzing PRR-associated genes.

Methods: We conducted a comparative analysis of PRR-associated gene expression in human peripheral blood mononuclear cells (PBMCs) infected with enterovirus 71 (EV-A71) which were derived from patients with HFMD of different severities and at different stages. A total of 30 PRR-associated genes were identified as significantly upregulated both over time and across different EV-A71 isolates. Subsequently, ELISA was employed to quantify the expression of the six most prominent genes among these 30 identified genes, specifically, BST2, IRF7, 1FI16, TRIM21, MX1, and DDX58.

Results: Compared with those at the recovery stage, the expression levels of BST2 (P=0.027), IFI16 (P=0.016), MX1 (P=0.046) and DDX58 (P=0.008) in the acute stage of infection were significantly upregulated, while no significant difference in the expression levels of IRF7 (P=0.495) and TRIM21 (P=0.071) was found between different stages of the disease. The expression levels of BST2, IRF7, IFI16 and MX1 were significantly higher in children infected with single pathogen than those infected with mixed pathogens, and BST2, IRF7, IFI16 and MX1 expression levels were significantly lower in coxsackie B virus (COXB) positive patients than the negative patients. Expression levels of one or more of BST2, IRF7, IFI16, TRIM21, MX1 and DDX58 genes were correlated with PCT levels, various white blood cell counts, and serum antibody levels that reflect disease course of HFMD. Aspartate aminotransferase was correlated with BST2, MX1 and DDX58 expression levels.

Conclusions: PRR-associated genes likely initiate the immune response in patients at the acute stage of HFMD.

Keywords

Pattern recognition receptors (PRRs) / Hand / foot / and mouth disease (HFMD) / Immune / Enterovirus 71 (EV-A71)

Cite this article

Download citation ▾
Muqi Wang, Huiling Deng, Yuan Chen, Yikai Wang, Yufeng Zhang, Chenrui Liu, Meng Zhang, Ting Li, Shuangsuo Dang, Yaping Li. Expression and clinical significance of pattern recognition receptor-associated genes in hand, foot and mouth disease. Asian Pacific Journal of Tropical Medicine, 2024, 17 (4) : 173-183 DOI:10.4103/apjtm.apjtm_876_23

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

Li XW, Ni X, Qian SY, Wang Q, Jiang RM, Xu WB, et al. Chinese guidelines for the diagnosis and treatment of hand, foot and mouth disease (2018 edition). World J Pediatr 2018; 14: 437-447.

[2]

Chang LY. Enterovirus 71 in Taiwan. Pediatr Neonatol 2008; 49(4): 103-112.

[3]

Zhang W, Huang Z, Huang M, Zeng J. Predicting severe enterovirus 71-infected hand, foot, and mouth disease: Cytokines and chemokines. Mediators Inflamm 2020; article ID: 9273241.

[4]

Chen BS, Lee HC, Lee KM, Gong YN, Shih SR. Enterovirus and encephalitis. Front Microbiol 2020; 11: 261.

[5]

Gu YY, Shi K, Yao S, Yang X, Liu YH, Tang L, et al. Morphological characteristics of fatal pediatric hand, foot and mouth disease: A clinicopathological study with related receptors of EV71. Pathol Res Pract 2017; 213(9): 1144-1151.

[6]

Lai RH, Chow YH, Chung NH, Chen TC, Shie FS, Juang JL. Neurotropic EV71 causes encephalitis by engaging intra-cellular TLR9 to elicit neurotoxic IL12-p40-iNOS signaling. Cell Death Dis 2022; 13: 328.

[7]

Li M, Li YP, Deng HL, Wang MQ, Chen Y, Zhang YF, et al. DNA methylation and SNP in IFITM3 are correlated with hand, foot and mouth disease caused by enterovirus 71. Int J Infect Dis 2021; 105: 199-208.

[8]

Li YP, Liu CR, Deng HL, Wang MQ, Tian Y, Chen Y, et al. DNA methylation and single-nucleotide polymorphisms in DDX58 are associated with hand, foot and mouth disease caused by enterovirus 71. PloS Negl Trop Dis 2022; 16: e0010090.

[9]

Li YP, Wang MQ, Liu CR, Deng HL, Wu Y, Dang SS, et al. Polymorphisms in the DC-SIGN gene and their association with the severity of hand, foot, and mouth disease caused by enterovirus 71. Arch Virol 2021; 166: 1133-1140.

[10]

Yuki K, Koutsogiannaki S. Pattern recognition receptors as therapeutic targets for bacterial, viral and fungal sepsis. Int Immunopharmacol 2021; 98: 107909.

[11]

Chen KR, Ling P. Interplays between enterovirus A71 and the innate immune system. J Biomed Sci 2019; 26: 95.

[12]

Tee HK, Zainol MI, Sam IC, Chan YF. Recent advances in the understanding of enterovirus A71 infection: A focus on neuropathogenesis. Expert Rev Anti Infect Ther 2021; 19: 733-747.

[13]

Cui D, Zhong F, Lin J, Wu Y, Long Q, Yang X, et al. Changes of circulating Th22 cells in children with hand, foot, and mouth disease caused by enterovirus 71 infection. Oncotarget 2017; 8: 29370-29382.

[14]

Zhao MQ, Wang LH, Lian GW, Lin ZF, Li YH, Guo M, et al. Characterization of lymphocyte subsets in peripheral blood cells of children with EV71 infection. J Microbiol Immunol Infect 2020; 53(5): 705-714.

[15]

Xie J, Jiao Y, Qiu Z, Li Q, Li T. Significant elevation of B cells at the acute stage in enterovirus 71-infected children with central nervous system involvement. Scand J Infect Dis 2010; 42: 931-935.

[16]

Jin Y, Zhang R, Wu W, Duan G. Antiviral and inflammatory cellular signaling associated with Enterovirus 71 infection. Viruses 2018; 10: 155.

[17]

Zhang X, Xu H, Chen X, Li X, Wang X, Ding S, et al. Association of functional polymorphisms in the MxA gene with susceptibility to enterovirus 71 infection. Hum Genet 2014; 133(2): 187-197.

[18]

Bruning AH, van der Sanden SM, ten Hoedt AE, Wolthers KC, van Kaam AH, Pajkrt D. An atypical course of cox-sackievirus A6 associated hand, foot and mouth disease in extremely low birth weight preterm twins. J Clin Virol 2015; 65: 20-22.

[19]

Qiu J, Yan H, Cheng N, Lu X, Hu X, Liang L, et al. The clinical and epidemiological study of children with hand, foot, and mouth disease in Hunan, China from 2013 to 2017. Sci Rep 2019; 9: 11662.

[20]

Li Y, Wang M, Wang W, Feng D, Deng H, Zhang Y, et al. Prognostic value of neutrophil-to-lymphocyte ratio in predicting death risk in patients with severe hand, foot and mouth disease. Ther Clin Risk Manag 2020; 16: 1023-1029.

[21]

Miao L, Liu Y, Luo P, Mao S, Liu J, Lu S. Association between platelet count and the risk and progression of hand, foot, and mouth disease among children. Clinics (Sao Paulo) 2020; 75: e1619.

[22]

Yi Z, Pei S, Suo W, Wang X, Huang Z, Yi A, et al. Epidemiological char-acteristics, routine laboratory diagnosis, clinical signs and risk factors for hand, -foot -and -mouth disease: A systematic review and meta-analysis. PLoS One 2022; 17: e0267716.

[23]

Zhou H, Guo SZ, Zhou H, Zhu YF, Zhang LJ, Zhang W. Clinical characteristics of hand, foot and mouth disease in Harbin and the prediction of severe cases. Chin Med J (Engl) 2012; 125: 1261-1265.

[24]

Wang C, Chen Y, Xu T, Tian X, Zheng J, Liu W, et al. A novel method to diagnose the infection of enterovirus A71 in children by detecting IgA from saliva. J Med Virol 2020; 92: 1059-1064.

[25]

Zheng B, Zhang J, Zheng T, Wang H, Li Z, Huan C, et al. ATP1B3 cooperates with BST-2 to promote hepatitis B virus restriction. J Med Virol 2020; 92: 201-209.

[26]

Jiang Z, Wei F, Zhang Y, Wang T, Gao W, Yu S, et al. IFI16 directly senses viral RNA and enhances RIG-I transcription and activation to restrict influenza virus infection. Nat Microbiol 2021; 6: 932-945.

[27]

Yang D, Wang X, Gao H, Chen B, Si C, Wang S. Downregulation of miR-155-5p facilitates enterovirus 71 replication through suppression of type I IFN response by targeting FOXO3/IRF7 pathway. Cell Cycle 2020; 19: 179-192.

[28]

Zou R, Zhang G, Li S, Wang W, Yuan J, Li J, et al. A functional poly-morphism in IFNAR1 gene is associated with susceptibility and severity of HFMD with EV71 infection. Sci Rep 2015; 5: 18541.

[29]

Brisse M, Ly H. Comparative structure and function analysis of the RIG-I-Like receptors: RIG-I and MDA5. Front Immunol 2019; 10: 1586.

[30]

Yang L, Liu X, Zhang L, Li X, Zhang X, Niu G, et al. Porcine TRIM21 enhances porcine circovirus 2 infection and host immune responses, but inhibits apoptosis of PCV2-infected cells. Viruses 2022; 14: 156.

PDF (2306KB)

4

Accesses

0

Citation

Detail

Sections
Recommended

/