Browse > Article
http://dx.doi.org/10.4196/kjpp.2014.18.3.225

The Protective Role of TLR3 and TLR9 Ligands in Human Pharyngeal Epithelial Cells Infected with Influenza A Virus  

Han, Yan (Dalian Center for Disease Control and Prevention)
Bo, Zhi-Jian (Dalian Center for Disease Control and Prevention)
Xu, Ming-Yu (Dalian Center for Disease Control and Prevention)
Sun, Nan (Dalian Center for Disease Control and Prevention)
Liu, Dan-Hong (Dalian Center for Disease Control and Prevention)
Publication Information
The Korean Journal of Physiology and Pharmacology / v.18, no.3, 2014 , pp. 225-231 More about this Journal
Abstract
In this study we aim to extensively investigate the anti-influenza virus immune responses in human pharyngeal epithelial cell line (Hep-2) and evaluate the protective role of Toll-like receptor (TLR) ligands in seasonal influenza A H1N1 (sH1N1) infections in vitro. We first investigated the expression of the TLRs and cytokines genes in resting and sH1N1 infected Hep-2 cells. Clear expressions of TLR3, TLR9, interleukin (IL)-6, tumour necrosis factor (TNF)-${\alpha}$ and interferon (IFN)-${\beta}$ were detected in resting Hep-2 cells. After sH1N1 infection, a ten-fold of TLR3 and TLR9 were elicited. Concomitant with the TLRs activation, transcriptional expression of IL-6, TNF-${\alpha}$ and IFN-${\beta}$ were significantly induced in sH1N1-infected cells. Pre-treatment of cells with poly I:C (an analog of viral double-stranded RNA) and CpG-ODN (a CpG-motif containing oligodeoxydinucleotide) resulted in a strong reduction of viral and cytokines mRNA expression. The results presented indicated the innate immune response activation in Hep-2 cells and affirm the antiviral role of Poly I:C and CpG-ODN in the protection against seasonal influenza A viruses.
Keywords
Human pharyngeal epithelial cell; Influenza A virus; Innate immune response; TLR ligands;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
연도 인용수 순위
1 Treanor JD. Influenza--the goal of control. N Engl J Med. 2007 4;357:1439-1441.   DOI   ScienceOn
2 Whitley RJ, Monto AS. Prevention and treatment of influenza in high-risk groups: children, pregnant women, immunocompromised hosts, and nursing home residents. J Infect Dis. 2006;194 Suppl 2:S133-138.   DOI
3 Nayak DP, Hui EK, Barman S. Assembly and budding of influenza virus. Virus Res. 2004;106:147-165.   DOI   ScienceOn
4 Centers for Disease Control and Prevention (CDC). Prevention and control of seasonal influenza with vaccines. Recommendations of the Advisory Committee on Immunization Practices-- United States, 2013-2014. MMWR Recomm Rep. 2013; 62:1-43.
5 Couch RB. Prevention and treatment of influenza. N Engl J Med. 2000;343:1778-1787.   DOI   ScienceOn
6 Taubenberger JK, Kash JC. Influenza virus evolution, host adaptation, and pandemic formation. Cell Host Microbe. 2010; 7:440-451.   DOI   ScienceOn
7 Julkunen I, Sareneva T, Pirhonen J, Ronni T, Melen K, Matikainen S. Molecular pathogenesis of influenza A virus infection and virus-induced regulation of cytokine gene expression. Cytokine Growth Factor Rev. 2001;12:171-180.   DOI   ScienceOn
8 Kawai T, Akira S. Innate immune recognition of viral infection. Nat Immunol. 2006;7:131-137.
9 Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol. 2010;11:373-384.   DOI   ScienceOn
10 Klinman DM. Immunotherapeutic uses of CpG oligodeoxynucleotides. Nat Rev Immunol. 2004;4:249-258.   DOI   ScienceOn
11 Wong JP, Christopher ME, Viswanathan S, Karpoff N, Dai X, Das D, Sun LQ, Wang M, Salazar AM. Activation of toll-like receptor signaling pathway for protection against influenza virus infection. Vaccine. 2009;27:3481-3483.   DOI   ScienceOn
12 Li H, Zhang J, Kumar A, Zheng M, Atherton SS, Yu FS. Herpes simplex virus 1 infection induces the expression of proinflammatory cytokines, interferons and TLR7 in human corneal epithelial cells. Immunology. 2006;117:167-176.   DOI   ScienceOn
13 Wang Y, Shan C, Ming S, Liu Y, Du Y, Jiang G. Immunoadjuvant effects of bacterial genomic DNA and CpG oligodeoxynucleotides on avian influenza virus subtype H5N1 inactivated oil emulsion vaccine in chicken. Res Vet Sci. 2009; 86:399-405.   DOI   ScienceOn
14 Le Goffic R, Pothlichet J, Vitour D, Fujita T, Meurs E, Chignard M, Si-Tahar M. Cutting Edge: Influenza A virus activates TLR3-dependent inflammatory and RIG-I-dependent antiviral responses in human lung epithelial cells. J Immunol. 2007; 178:3368-3372.   DOI
15 Li J, Jeong MY, Bae JH, Shin YH, Jin M, Hang SM, Lee JC, Lee SJ, Park K. Toll-like receptor3-mediated induction of chemokines in salivary epithelial cells. Korean J Physiol Pharmacol. 2010;14:235-240.   DOI   ScienceOn
16 Samuel CE. Antiviral actions of interferons. Clin Microbiol Rev. 2001;14:778-809.   DOI   ScienceOn
17 Kaiser L, Fritz RS, Straus SE, Gubareva L, Hayden FG. Symptom pathogenesis during acute influenza: interleukin-6 and other cytokine responses. J Med Virol. 2001;64:262-268.   DOI   ScienceOn
18 Eccles R. Understanding the symptoms of the common cold and influenza. Lancet Infect Dis. 2005;5:718-725.   DOI   ScienceOn
19 Rimmelzwaan GF, Baars M, van Beek R, van Amerongen G, Lovgren-Bengtsson K, Claas EC, Osterhaus AD. Induction of protective immunity against influenza virus in a macaque model: comparison of conventional and iscom vaccines. J Gen Virol. 1997;78:757-765.   DOI
20 Xie H, Raybourne RB, Babu US, Lillehoj HS, Heckert RA. CpG-induced immunomodulation and intracellular bacterial killing in a chicken macrophage cell line. Dev Comp Immunol. 2003;27:823-834.   DOI   ScienceOn
21 de Jong MD, Simmons CP, Thanh TT, Hien VM, Smith GJ, Chau TN, Hoang DM, Chau NV, Khanh TH, Dong VC, Qui PT, Cam BV, Ha do Q, Guan Y, Peiris JS, Chinh NT, Hien TT, Farrar J. Fatal outcome of human influenza A (H5N1) is associated with high viral load and hypercytokinemia. Nat Med. 2006;12:1203-1207.   DOI   ScienceOn
22 Kash JC, Tumpey TM, Proll SC, Carter V, Perwitasari O, Thomas MJ, Basler CF, Palese P, Taubenberger JK, García-Sastre A, Swayne DE, Katze MG. Genomic analysis of increased host immune and cell death responses induced by 1918 influenza virus. Nature. 2006;443:578-581.
23 Li IW, Chan KH, To KW, Wong SS, Ho PL, Lau SK, Woo PC, Tsoi HW, Chan JF, Cheng VC, Zheng BJ, Chen H, Yuen KY. Differential susceptibility of different cell lines to swine-origin influenza A H1N1, seasonal human influenza A H1N1, and avian influenza A H5N1 viruses. J Clin Virol. 2009;46:325-330.   DOI   ScienceOn
24 Sen GC, Sarkar SN. Transcriptional signaling by double stranded RNA: role of TLR3. Cytokine Growth Factor Rev. 2005;16:1-24.   DOI   ScienceOn
25 Seo SH, Webster RG. Tumor necrosis factor alpha exerts powerful anti-influenza virus effects in lung epithelial cells. J Virol. 2002;76:1071-1076.   DOI
26 Zu M, Yang F, Zhou W, Liu A, Du G, Zheng L. In vitro anti-influenza virus and anti-inflammatory activities of theaflavin derivatives. Antiviral Res. 2012;94:217-224.   DOI   ScienceOn
27 Bauer RN, Brighton LE, Mueller L, Xiang Z, Rager JE, Fry RC, Peden DB, Jaspers I. Influenza enhances caspase-1 in bronchial epithelial cells from asthmatic volunteers and is associated with pathogenesis. J Allergy Clin Immunol. 2012; 130:958-967.   DOI   ScienceOn
28 Kaiser L, Fritz RS, Straus SE, Gubareva L, Hayden FG. Symptom pathogenesis during acute influenza: interleukin-6 and other cytokine responses. J Med Virol. 2001;64:262-268.   DOI   ScienceOn
29 Svitek N, Rudd PA, Obojes K, Pillet S, von Messling V. Severe seasonal influenza in ferrets correlates with reduced interferon and increased IL-6 induction. Virology. 2008;376:53-59.   DOI   ScienceOn
30 Brydon EW, Morris SJ, Sweet C. Role of apoptosis and cytokines in influenza virus morbidity. FEMS Microbiol Rev. 2005;29:837-850.   DOI   ScienceOn
31 Tisoncik JR, Korth MJ, Simmons CP, Farrar J, Martin TR, Katze MG. Into the eye of the cytokine storm. Microbiol Mol Biol Rev. 2012;76:16-32.   DOI
32 Cheng XW, Lu J, Wu CL, Yi LN, Xie X, Shi XD, Fang SS, Zan H, Kung HF, He ML. Three fatal cases of pandemic 2009 influenza A virus infection in Shenzhen are associated with cytokine storm. Respir Physiol Neurobiol. 2011;175:185-187.   DOI   ScienceOn
33 Kanzler H, Barrat FJ, Hessel EM, Coffman RL. Therapeutic targeting of innate immunity with Toll-like receptor agonists and antagonists. Nat Med. 2007;13:552-559.   DOI   ScienceOn
34 Miller M, Viboud C, Simonsen L, Olson DR, Russell C. Mortality and morbidity burden associated with A/H1N1pdm influenza virus: Who is likely to be infected, experience clinical symptoms, or die from the H1N1pdm 2009 pandemic virus? Version 2. PLoS Curr. 2009;1:RRN1013.
35 Koerner I, Kochs G, Kalinke U, Weiss S, Staeheli P. Protective role of beta interferon in host defense against influenza A virus. J Virol. 2007;81:2025-2030.   DOI   ScienceOn
36 Kido H, Okumura Y, Takahashi E, Pan HY, Wang S, Chida J, Le TQ, Yano M. Host envelope glycoprotein processing proteases are indispensable for entry into human cells by seasonal and highly pathogenic avian influenza viruses. J Mol Genet Med. 2008;3:167-175.