Inflammation Research

, Volume 58, Issue 9, pp 585–592 | Cite as

Rotavirus and coxsackievirus infection activated different profiles of toll-like receptors and chemokines in intestinal epithelial cells

Original Research Paper



To understand the inflammatory-immune response in intestinal epithelial cells after infection of rotavirus and coxsackievirus B3.


We examined by quantitative PCR the expression profiles of genes encoding five toll-like receptors (TLR) and levels of three chemokines in response to rotavirus and coxsackievirus B3 infection in a human intestinal epithelial cell line (HT-29 cells).


We demonstrated that rotavirus induced significantly increased levels of mRNA expression for TLR2, TLR3, TLR7 and TLR8 in HT-29 cells in a time-dependent manner. In contrast, coxsackievirus B3 did not stimulate mRNA expression for TLR3. Rotavirus and coxsackievirus B3 also induced higher levels of mRNA expression for RANTES, IP-10 and IL-8 during the period of infection in a different manner. Finally, significantly elevated levels of RANTES, IP-10 and IL-8 were detected by ELISA in rotavirus-infected cells from 24 to 48 h.


Our findings suggest that different patterns of TLRs and chemokines were induced in the initiation and modulation of immune response to rotavirus and coxsackievirus B3 infection.


Rotavirus Coxsackievirus B3 TLR Chemokine 



This research was supported by a grant from Fudan University, China.

Conflict of interest statement

The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the funding agency.


  1. 1.
    Glass RI, Parashar UD, Bresee JS, Turdos R, Fischer TK, Widdowson MA, et al. Rotavirus vaccine: current prospects and future challenges. Lancet. 2006;368:323–32.PubMedCrossRefGoogle Scholar
  2. 2.
    Modlin JF, Rotbart HA. Group B coxsackie disease in children. Curr Top Microbiol Immunol. 1997;223:53–80.PubMedGoogle Scholar
  3. 3.
    Greenberg H, Clark H, Offit P. Rotavirus pathology and pathophysiology. Curr Top Microbiol Immunol. 1994;185:255–83.PubMedGoogle Scholar
  4. 4.
    Harrath R, Bourlet T, Delzay O, Douche-Aourik F, Omar S, Aouni M, et al. Coxsackievirus B3 replication and persistence in intestinal cells from mice infected orally and in the human CaCo-2 cell lines. J Med Virol. 2004;74:283–90.PubMedCrossRefGoogle Scholar
  5. 5.
    Akira S, Hemmi H. Recognition of pathogen-associated molecular patterns by TLR family. Immunol Lett. 2003;85:85–95.PubMedCrossRefGoogle Scholar
  6. 6.
    Bieback K, Lien E, Klagge I, Avota E, Schneider-Schaulies J, Duprex WP, et al. Hemagglutinin protein of wild-type measles virus activates toll-like receptor 2 signalling. J Virol. 2002;76:8729–36.PubMedCrossRefGoogle Scholar
  7. 7.
    Compon T, Kurton-Jones EA, Boehme KW, Belko J, Latz E, Golenbock DT, et al. Human cytomegalovirus activates inflammatory cytokine responses via CD14 and toll-like receptor 2. J Virol. 2003;77:4588–96.CrossRefGoogle Scholar
  8. 8.
    Echchannaoui H, Frei K, Schnell C, Leib SL, Zimmerli W, Landmann R. Toll-like receptor 2-deficient mice are highly susceptible to Streptococcus pneumoniae meningitis because of reduced bacterial clearing and enhanced inflammation. J Infect Dis. 2002;182:798–806.CrossRefGoogle Scholar
  9. 9.
    Koedel U, Angele B, Rupprecht T, Wagner H, Roggenkamp A, Pfister HW, et al. Toll-like receptor 2 participates in mediation of immune response in experimental pneumococcal meningitis. J Immunol. 2003;170:438–44.PubMedGoogle Scholar
  10. 10.
    Iwaki D, Mitsuazawa H, Murakami S. The extracellular toll-like receptor 2 domain directly binds peptidoglycan derived from Staphylococcus aureus. J Biol Chem. 2002;24:315–20.Google Scholar
  11. 11.
    Reiling N, Hölscher C, Fehrenbach A, Kröger S, Kirschning CJ, Goyert S, et al. Cutting edge: toll-like receptor (TLR) 2 and TLR4-mediated pathogen recognition in resistance to airborne infection with Mycobacterium tuberculosis. J Immunol. 2002;169:3480–4.PubMedGoogle Scholar
  12. 12.
    Takeuchi O, Hoshino K, Kawai T, Sanjo H, Takada H, Ogawa T, et al. Differential roles of TLR2 and TLR4 in recognition of Gram-negative and Gram-positive bacterial cell wall component. Immunity. 1999;11:443–51.PubMedCrossRefGoogle Scholar
  13. 13.
    Haeberle HA, Takizawa R, Casola A, Brasier AR, Dieterich H, van Rooijen N, et al. Respiratory syncytial virus-induced activation of nuclear factor-κB in the lung involves alveolar macrophages and toll-like receptor 4-dependent pathways. J Infect Dis. 2002;186:1199–206.PubMedCrossRefGoogle Scholar
  14. 14.
    Hornef MW, Normark BH, Vandewalle A, Normark S. Intracellular recognition of lipopolysacchride by toll-like receptor 4 in intestinal epithelial cells. J Exp Med. 2003;198:1225–35.PubMedCrossRefGoogle Scholar
  15. 15.
    Alexopoulou L, Holt AC, Medzhitov R, Flavell RA. Recognition of double-stranded RNA and activation of NF-kappaB by toll-like receptors. Nature. 2001;413:732–8.PubMedCrossRefGoogle Scholar
  16. 16.
    Heil F, Hemmi H, Hochrein H, Ampenberger F, Kirschning C, Akira S, et al. Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8. Science. 2004;303:1526–9.PubMedCrossRefGoogle Scholar
  17. 17.
    Lee J, Chuang TH, Redecke V, She L, Pitha PM, Carson DA, et al. Molecular basis for the immnuostimulatory activity of guanine nucleotide analogs: activation of toll-like receptor 7. Proc Natl Acad Sci. 2003;100:6646–51.PubMedCrossRefGoogle Scholar
  18. 18.
    Devora R, Zlotnik A. The biology of chemokines and their receptors. Annu Rev Immunol. 2000;18:217–42.CrossRefGoogle Scholar
  19. 19.
    Casola A, Estes MK, Crawford SE, Ogra PL, Ernst PB, Garofalo RP, et al. Rotavirus infection of cultured intestinal epithelial cells induces secretion of CXC and CC chemokines. Gastroenterology. 1999;114:947–55.CrossRefGoogle Scholar
  20. 20.
    Han RO, Ray PE, Baughman KL, Feldman AM. Detection of interleukin and interleukin-receptor mRNA in human heart by polymerase chain reaction. Biochem Biophys Res Commun. 1991;181:520–3.PubMedCrossRefGoogle Scholar
  21. 21.
    Hornsleth A, Loland L, Larsen LB. Cytokines and chemokines in respiratory secretion and severity of disease in infants with respiratory syncytial virus (RSV) infection. J Clin Virol. 2001;21:163–70.PubMedCrossRefGoogle Scholar
  22. 22.
    Zanone MM, Favaro E, Conaldi PG, Greening J, Bottelli A, Perin PC, et al. Persistent infection of human microvascular endothelial cells by coxsakie B viruses induces increased expression of adhesion molecules. J Immunol. 2003;171:438–46.PubMedGoogle Scholar
  23. 23.
    Heim A, Zeuke S, Weiss S, Ruschewski W, Grumbach IM. Transient induction of cytokine production in human myocardial fibroblasts by coxsackievirus B3. Circ Res. 2000;86:753–9.PubMedGoogle Scholar
  24. 24.
    Ward LA, Yuan L, Rosen BI, Saif LJ. Development of mucosal and systemic lymphoproliferative response and protective immunity to human group A rotavirus in a gnotobiotic pig model. Clin Diag Lab Immunol. 1996;3:342–50.Google Scholar
  25. 25.
    Xu J, Yang Y, Sun J, Ding Y, Su L, Shao C, et al. Expression of toll-like receptors and their association with cytokine responses in peripheral blood mononuclear cells of children with acute rotavirus diarrhea. Clin Exp Immunol. 2006;144:376–81.PubMedCrossRefGoogle Scholar
  26. 26.
    Guillot L, Goffic Le R, Bloch S, Escriou N, Akira S, Chignard M, et al. Involvement of toll-like receptor 3 in the immune response of lung epithelial cells to double-stranded RNA and influenza A virus. J Biol Chem. 2005;280:5571–80.PubMedCrossRefGoogle Scholar
  27. 27.
    Diebold SS, Kaisho T, Hemmi H, Akira S, Sousa CR. Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA. Science. 2004;303:1529–31.PubMedCrossRefGoogle Scholar
  28. 28.
    Lund JM, Alexopoulou L, Sato A, Karow M, Adams NC, Gale NW, et al. Recognition of single-stranded RNA by toll-like receptor 7. Proc Natl Acad Sci. 2004;101:5598–603.PubMedCrossRefGoogle Scholar
  29. 29.
    Triantafilou K, Orthopoulos G, Vakakis E, Ahmed MA, Golenbock DT, Lepper PM, et al. Human cardiac inflammatory responses triggered by Coxsackie B viruses are mainly toll-like receptor (TLR) 8-dependent. Cell Microbiol. 2005;7:1117–26.PubMedCrossRefGoogle Scholar
  30. 30.
    Burzyn D, Rassa JC, Kim D, Nepomnaschy I, Ross SR, Piazzon I. Toll-like receptor 4-dependent activation of dentritic cells by a retrovirus. J Virol. 2004;78:576–84.PubMedCrossRefGoogle Scholar
  31. 31.
    Kurt-Jones EA, Popova L, Kwinn L, Haynes LM, Jones LP, Tripp RA, et al. Pattern recognition receptors TLR4 and CD14 mediate response to respiratory syncytial virus. Nat Immunol. 2000;1:398–401.PubMedCrossRefGoogle Scholar
  32. 32.
    Monick MM, Yarovinsky TO, Powers LS, Butler NS, Carter AB, Gudmundsson G, et al. Respiratory syncytial virus up-regulates TLR4 and sensitizes airway epithelial cells to endotoxin. J Biol Chem. 2003;278:53035–44.PubMedCrossRefGoogle Scholar
  33. 33.
    Glass WG, Rosenberg HF, Murphy PM. Chemokine regulation of inflammation during acute viral infection. Curr Opin Allergy Clin Immunol. 2003;3:467–73.PubMedCrossRefGoogle Scholar
  34. 34.
    Liu PP, Mason JW. Advances in the understanding of myocarditis. Circulation. 2001;104:1076–82.PubMedCrossRefGoogle Scholar
  35. 35.
    Melchjorsen J, Sorensen LN, Paludan SR. Expression and function of chemokines during viral infections: from molecular mechanisms to in vivo function. J Leukocyte Biol. 2003;74:331–43.PubMedCrossRefGoogle Scholar
  36. 36.
    Olsson A, Johansson U, Korsgren O, Frisk G. Inflammatory gene expression in coxsackievirus B4-infected human islets of Langerhans. Biochem Biophys Res Commun. 2005;330:571–6.PubMedCrossRefGoogle Scholar
  37. 37.
    Wang Y, Dennehy PH, Keyserling HL, Tang K, Gentsch JR, Glass RI, et al. Rotavirus infection alters peripheral T-cell homeostasis in children with acute diarrhea. J Virol. 2007;81:3904–12.PubMedCrossRefGoogle Scholar
  38. 38.
    Rudd BD, Burstein E, Duckett CS, Li X, Lukacs NW. Differential role for TLR3 in respiratory syncytial virus-induced chemokine expression. J Virol. 2005;79:3350–7.PubMedCrossRefGoogle Scholar

Copyright information

© Birkhäuser Verlag, Basel/Switzerland 2009

Authors and Affiliations

  1. 1.Pediatric InstituteChildren’s Hospital, Fudan UniversityShanghaiChina
  2. 2.Gastroenteritis and Respiratory Virus Laboratory Branch, Division of Viral DiseasesCenters for Disease Control and PreventionAtlantaUSA

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