This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Azevedo, M. S. P.
Right arrow Articles by Saif, L. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Azevedo, M. S. P.
Right arrow Articles by Saif, L. J.

 Previous Article  |  Next Article 

Journal of Virology, January 2006, p. 372-382, Vol. 80, No. 1
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.1.372-382.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Cytokine Responses in Gnotobiotic Pigs after Infection with Virulent or Attenuated Human Rotavirus

M. S. P. Azevedo, L. Yuan, S. Pouly, A. M. Gonzales, K. I. Jeong, T. V. Nguyen, and L. J. Saif*

Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Department of Veterinary Preventive Medicine, The Ohio State University, Wooster, Ohio

Received 29 July 2005/ Accepted 13 October 2005

To understand the role of cytokines during rotavirus infection, we assessed the kinetics of tumor necrosis factor alpha (TNF-{alpha}) and interleukin-6 (IL-6) (proinflammatory), IL-12 (Th1 inducer), gamma interferon (IFN-{gamma}) (Th1), IL-4 and IL-10 (Th2), and transforming growth factor ß (Th3) cytokine responses by enzyme-linked immunosorbent assay in serum and intestinal contents of neonatal gnotobiotic pigs and IL-12, IFN-{gamma}, IL-4, and IL-10 cytokine-secreting cell (CSC) responses of mononuclear cells from ileum, spleen, and blood by ELISPOT. Pigs received the virulent Wa P1A[8]G1 strain of human rotavirus (HRV) (VirHRV), attenuated Wa HRV (AttHRV), or mock (controls). The TNF-{alpha} levels peaked earlier and remained elevated in serum of the VirHRV group but peaked later in the AttHRV group. In serum, IL-6 was significantly elevated at postinoculation day (PID) 1 in the VirHRV group and at PID 3 in both HRV groups. The IL-12 was detected in serum of all pigs including controls with significantly elevated peaks in both HRV-infected groups, indicating a role for IL-12 in the induction of immune responses to rotavirus infection. Only low and transient IFN-{gamma} responses occurred in serum and intestinal contents of the AttHRV-infected pigs, compared to significantly higher and prolonged IFN-{gamma} responses in the VirHRV-infected pigs. This observation coincides with the diarrhea and viremia induced by VirHRV. The number of IFN-{gamma}-secreting cells was significantly higher in the ileum of the VirHRV group than in that of the controls. The number of IL-4 CSCs was significantly higher in ileum of both HRV groups than in that of the controls. Significantly higher levels of IL-10 in the serum occurred early in the VirHRV group, compared to lower levels in the AttHRV group. However, the number of IL-10 CSCs was significantly higher later in ileum and spleen of the AttHRV than in the VirHRV group, suggesting a delayed initiation of a Th2 response induced by AttHRV. A significantly higher percentage of pigs had IFN-{gamma} and IL-10 responses in serum after VirHRV infection than after AttHRV infection or in controls. These data indicate a balanced Th1/Th2 response during rotavirus infection, with higher cytokine levels early after infection with VirHRV compared to that with AttHRV. Mapping the kinetics and patterns of cytokine responses after rotavirus infection has important implications for induction of protective immunity by HRV vaccines. Higher protection rates may be associated with more balanced Th1- and Th2-type responses, but induction of higher earlier IFN-{gamma} (Th1) and proinflammatory cytokines triggered by VirHRV may also play an important role in the higher intestinal immunoglobulin A responses and protection rates induced by VirHRV.

* Corresponding author. Mailing address: Food Animal Health Research Program, Ohio Agricultural Research and Development Center, The Ohio State University, 1680 Madison Avenue, Wooster, OH 44691. Phone: (330) 263-3744. Fax: (330) 263-3677. E-mail: saif.2{at}osu.edu.

Journal of Virology, January 2006, p. 372-382, Vol. 80, No. 1
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.1.372-382.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Jung, K., Renukaradhya, G. J., Alekseev, K. P., Fang, Y., Tang, Y., Saif, L. J. (2009). Porcine reproductive and respiratory syndrome virus modifies innate immunity and alters disease outcome in pigs subsequently infected with porcine respiratory coronavirus: implications for respiratory viral co-infections. J. Gen. Virol. 90: 2713-2723 [Abstract] [Full Text]  
  • Vaarala, O., Atkinson, M. A., Neu, J. (2008). The "Perfect Storm" for Type 1 Diabetes: The Complex Interplay Between Intestinal Microbiota, Gut Permeability, and Mucosal Immunity. Diabetes 57: 2555-2562 [Abstract] [Full Text]  
  • Sugata, K., Taniguchi, K., Yui, A., Miyake, F., Suga, S., Asano, Y., Ohashi, M., Suzuki, K., Nishimura, N., Ozaki, T., Yoshikawa, T. (2008). Analysis of Rotavirus Antigenemia and Extraintestinal Manifestations in Children With Rotavirus Gastroenteritis. Pediatrics 122: 392-397 [Abstract] [Full Text]  
  • Rogers, C. S., Abraham, W. M., Brogden, K. A., Engelhardt, J. F., Fisher, J. T., McCray, P. B. Jr., McLennan, G., Meyerholz, D. K., Namati, E., Ostedgaard, L. S., Prather, R. S., Sabater, J. R., Stoltz, D. A., Zabner, J., Welsh, M. J. (2008). The porcine lung as a potential model for cystic fibrosis. Am. J. Physiol. Lung Cell. Mol. Physiol. 295: L240-L263 [Abstract] [Full Text]  
  • Graham, K. L., Sanders, N., Tan, Y., Allison, J., Kay, T. W. H., Coulson, B. S. (2008). Rotavirus Infection Accelerates Type 1 Diabetes in Mice with Established Insulitis. J. Virol. 82: 6139-6149 [Abstract] [Full Text]  
  • Zhang, X., Alekseev, K., Jung, K., Vlasova, A., Hadya, N., Saif, L. J. (2008). Cytokine Responses in Porcine Respiratory Coronavirus-Infected Pigs Treated with Corticosteroids as a Model for Severe Acute Respiratory Syndrome. J. Virol. 82: 4420-4428 [Abstract] [Full Text]  
  • Souza, M., Azevedo, M. S. P., Jung, K., Cheetham, S., Saif, L. J. (2008). Pathogenesis and Immune Responses in Gnotobiotic Calves after Infection with the Genogroup II.4-HS66 Strain of Human Norovirus. J. Virol. 82: 1777-1786 [Abstract] [Full Text]  
  • Souza, M., Cheetham, S. M., Azevedo, M. S. P., Costantini, V., Saif, L. J. (2007). Cytokine and Antibody Responses in Gnotobiotic Pigs after Infection with Human Norovirus Genogroup II.4 (HS66 Strain). J. Virol. 81: 9183-9192 [Abstract] [Full Text]  
  • Beau, I., Cotte-Laffitte, J., Amsellem, R., Servin, A. L. (2007). A Protein Kinase A-Dependent Mechanism by Which Rotavirus Affects the Distribution and mRNA Level of the Functional Tight Junction-Associated Protein, Occludin, in Human Differentiated Intestinal Caco-2 Cells. J. Virol. 81: 8579-8586 [Abstract] [Full Text]  
  • Rhoads, J. M., Corl, B. A., Harrell, R., Niu, X., Gatlin, L., Phillips, O., Blikslager, A., Moeser, A., Wu, G., Odle, J. (2007). Intestinal ribosomal p70S6K signaling is increased in piglet rotavirus enteritis. Am. J. Physiol. Gastrointest. Liver Physiol. 292: G913-G922 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»