Journal
VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY
Volume 141, Issue 3-4, Pages 258-266Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.vetimm.2011.03.014
Keywords
Crohn's disease; Johne's disease; Mycobacterium avium subsp.; paratuberculosis; Animal model; Flow cytometry; Cytokines
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Funding
- National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services [N01-AI-30055]
- JDIP program (USDA-CSREES-NRI-CAP) [2007-01019]
- USDA-NRI [2005-35204-16106]
- Johne's disease Integrated Program [USDA-CSREES 2008-55620-18710]
- WSU Monoclonal Antibody Center
- Egyptian Educational Bureau
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Mycobacterium avium subsp. paratuberculosis (Map), the etiologic agent of Johne's disease (JD) in ruminants, has been implicated in the pathogenesis of Crohn's disease (CD) in humans. We developed a bovine ileal cannulation model to facilitate comparison of the immune response to Map and the mechanisms of pathogenesis in cattle and humans. Initial studies showed a T cannula could be maintained for up to a year in calves without inducing inflammation or adversely affecting intestinal function. Map introduced through the cannula established a persistent low level of infection without inflammation. Infection elicited an immune response to Map antigens detectable by flow cytometry. Further studies now show the cannulation model can be used with cows during the later stage of infection, affording access to the target tissue at all stages of infection. The studies also revealed no difference in infectivity or immunogenicity of isolates of Map obtained from cattle or humans with CD. Comparison of the immune response to Map during the early and late stages of infection using PCR, flow cytometry and QRT-PCR, showed the immune response early in the disease process is dominated by CD4 T cells. A CD8 response is delayed but comparable at later stages of infection. Genes for pro-inflammatory cytokines IFN-gamma and the recently identified genes encoding IL-17 and IL-22 are up regulated in infected animals. These findings reveal that both human and bovine isolates of Map can establish infection and induce similar immune responses in a bovine model. They also reveal the cytokine responses elicited in cattle are similar to those implicated in CD pathogenesis. (C) 2011 Elsevier B.V. All rights reserved.
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