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 Coussens, P. M.
Right arrow Articles by McNulty, A. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Coussens, P. M.
Right arrow Articles by McNulty, A. M.

 Previous Article  |  Next Article 

Infection and Immunity, March 2004, p. 1409-1422, Vol. 72, No. 3
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.3.1409-1422.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Cytokine Gene Expression in Peripheral Blood Mononuclear Cells and Tissues of Cattle Infected with Mycobacterium avium subsp. paratuberculosis: Evidence for an Inherent Proinflammatory Gene Expression Pattern

Paul M. Coussens,* Nitin Verman, Marc A. Coussens, Michael D. Elftman, and Amanda M. McNulty

Department of Animal Science and Center for Animal Functional Genomics, Michigan State University, East Lansing Michigan 48824

Received 25 August 2003/ Returned for modification 12 November 2003/ Accepted 20 November 2003

In cattle and other ruminants, infection with the intracellular pathogen Mycobacterium avium subsp. paratuberculosis results in a granulomatous enteritis (Johne's disease) that is often fatal. The key features of host immunity to M. avium subsp. paratuberculosis infection include an appropriate early proinflammatory and cytotoxic response (Th1-like) that eventually gives way to a predominant antibody-based response (Th2-like). Clinical disease symptoms often appear subsequent to waning of the Th1-like immune response. Understanding why this shift in the immune response occurs and the underlying molecular mechanisms involved is critical to future control measures and diagnosis. Previous studies have suggested that M. avium subsp. paratuberculosis may suppress gene expression in peripheral blood mononuclear cells (PBMCs) from infected cows, despite a continued inflammatory reaction at sites of infection. In the present study, we tested the hypothesis that exposure to M. avium subsp. paratuberculosis suppresses a proinflammatory gene expression pattern in PBMCs from infected cows. To do this, we examined expression of genes encoding interleukin-1{alpha} (IL-1{alpha}), IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p35, IL-16, and IL-18, as well as genes encoding gamma interferon (IFN-{gamma}), transforming growth factor ß (TGF-ß), and tumor necrosis factor alpha (TNF-{alpha}), in PBMCs, intestinal lesions, and mesenteric lymph nodes of cattle naturally infected with M. avium subsp. paratuberculosis. Cytokine gene expression in these cells and tissues was compared to expression in similar cells and tissues from control uninfected cattle. Our comprehensive results demonstrate that for most cytokine genes, including the genes encoding IFN-{gamma}, TGF-ß, TNF-{alpha}, IL-1{alpha}, IL-4, IL-6, IL-8, and IL-12p35, differential expression in PBMCs from infected and control cattle did not require stimulation with M. avium subsp. paratuberculosis. In fact, stimulation with M. avium subsp. paratuberculosis tended to reduce the differential expression observed in infected and uninfected cows for genes encoding IFN-{gamma}, IL-1{alpha}, and IL-6. Only IL-10 gene expression was consistently enhanced by M. avium subsp. paratuberculosis stimulation of PBMCs from subclinically infected cattle. In ileal tissues from M. avium subsp. paratuberculosis-infected cattle, expression of the genes encoding IFN-{gamma}, TGF-ß, IL-5, and IL-8 was greater than the expression in comparable tissues from control uninfected cattle, while expression of the gene encoding IL-16 was lower in tissues from infected cattle than in control tissues. Mesenteric lymph nodes draining sites of M. avium subsp. paratuberculosis infection expressed higher levels of IL-1{alpha}, IL-8, IL-2, and IL-10 mRNA than similar tissues from control uninfected cattle expressed. In contrast, the genes encoding TGF-ß and IL-16 were expressed at lower levels in lymph nodes from infected cattle than in tissues from uninfected cattle. Taken together, our results suggest that cells or other mechanisms capable of limiting proinflammatory responses to M. avium subsp. paratuberculosis develop in infected cattle and that a likely place for development and expansion of these cell populations is the mesenteric lymph nodes draining sites of infection.

* Corresponding author. Mailing address: Department of Animal Science, 1205H Anthony Hall, Michigan State University, East Lansing, MI 48824. Phone: (517) 353-3158. Fax: (517) 353-1699. E-mail: coussens{at}msu.edu.

Editor: B. B. Finlay

Infection and Immunity, March 2004, p. 1409-1422, Vol. 72, No. 3
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.3.1409-1422.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Laspiur, J. P., Burton, J. L., Weber, P. S. D., Moore, J., Kirkwood, R. N., Trottier, N. L. (2009). Dietary Protein Intake and Stage of Lactation Differentially Modulate Amino Acid Transporter mRNA Abundance in Porcine Mammary Tissue. J. Nutr. 139: 1677-1684 [Abstract] [Full Text]  
  • Piper, E. K., Jonsson, N. N., Gondro, C., Lew-Tabor, A. E., Moolhuijzen, P., Vance, M. E., Jackson, L. A. (2009). Immunological Profiles of Bos taurus and Bos indicus Cattle Infested with the Cattle Tick, Rhipicephalus (Boophilus) microplus. CVI 16: 1074-1086 [Abstract] [Full Text]  
  • Worku, M., Morris, A. (2009). Binding of different forms of lipopolysaccharide and gene expression in bovine blood neutrophils. J DAIRY SCI 92: 3185-3193 [Abstract] [Full Text]  
  • Khare, S., Nunes, J. S., Figueiredo, J. F., Lawhon, S. D., Rossetti, C. A., Gull, T., Rice-Ficht, A. C., Adams, L. G. (2009). Early Phase Morphological Lesions and Transcriptional Responses of Bovine Ileum Infected with Mycobacterium avium subsp. paratuberculosis. Vet Pathol 46: 717-728 [Abstract] [Full Text]  
  • Karcher, E. L., Bayles, D. O., Bannantine, J. P., Beitz, D. C., Stabel, J. R. (2008). Osteopontin: A Novel Cytokine Involved in the Regulation of Mycobacterium avium subspecies paratuberculosis Infection in Periparturient Dairy Cattle. J DAIRY SCI 91: 3079-3091 [Abstract] [Full Text]  
  • Robinson, M., O'Brien, R., Mackintosh, C., Griffin, F. (2008). Differential Immune Responses of Red Deer (Cervus elaphus) following Experimental Challenge with Mycobacterium avium subsp. paratuberculosis. CVI 15: 963-969 [Abstract] [Full Text]  
  • Scanu, A. M., Bull, T. J., Cannas, S., Sanderson, J. D., Sechi, L. A., Dettori, G., Zanetti, S., Hermon-Taylor, J. (2007). Mycobacterium avium Subspecies paratuberculosis Infection in Cases of Irritable Bowel Syndrome and Comparison with Crohn's Disease and Johne's Disease: Common Neural and Immune Pathogenicities. J. Clin. Microbiol. 45: 3883-3890 [Abstract] [Full Text]  
  • Wu, C.-w., Livesey, M., Schmoller, S. K., Manning, E. J. B., Steinberg, H., Davis, W. C., Hamilton, M. J., Talaat, A. M. (2007). Invasion and Persistence of Mycobacterium avium subsp. paratuberculosis during Early Stages of Johne's Disease in Calves. Infect. Immun. 75: 2110-2119 [Abstract] [Full Text]  
  • Murphy, J. T., Sommer, S., Kabara, E. A., Verman, N., Kuelbs, M. A., Saama, P., Halgren, R., Coussens, P. M. (2006). Gene expression profiling of monocyte-derived macrophages following infection with Mycobacterium avium subspecies avium and Mycobacterium avium subspecies paratuberculosis. Physiol. Genomics 28: 67-75 [Abstract] [Full Text]  
  • Motiwala, A. S., Janagama, H. K., Paustian, M. L., Zhu, X., Bannantine, J. P., Kapur, V., Sreevatsan, S. (2006). Comparative Transcriptional Analysis of Human Macrophages Exposed to Animal and Human Isolates of Mycobacterium avium Subspecies paratuberculosis with Diverse Genotypes.. Infect. Immun. 74: 6046-6056 [Abstract] [Full Text]  
  • Ruby, T., Whittaker, C., Withers, D. R., Chelbi-Alix, M. K., Morin, V., Oudin, A., Young, J. R., Zoorob, R. (2006). Transcriptional profiling reveals a possible role for the timing of the inflammatory response in determining susceptibility to a viral infection.. J. Virol. 80: 9207-9216 [Abstract] [Full Text]  
  • Thacker, T. C., Palmer, M. V., Waters, W. R. (2006). Correlation of Cytokine Gene Expression with Pathology in White-Tailed Deer (Odocoileus virginianus) Infected with Mycobacterium bovis. CVI 13: 640-647 [Abstract] [Full Text]  
  • Coussens, P. M. (2004). Model for Immune Responses to Mycobacterium avium Subspecies paratuberculosis in Cattle. Infect. Immun. 72: 3089-3096 [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»