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-γ 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.
Bibliographical noteFunding Information:
This project was funded in part with funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services , under Contract No. N01-AI-30055 , the JDIP program ( USDA-CSREES-NRI-CAP Award No. 2007-01019 ) awarded to W.C.D., USDA-NRI grant ( 2005-35204-16106 ) and Johne's disease Integrated Program ( USDA-CSREES 2008-55620-18710 ) awarded to SS and the WSU Monoclonal Antibody Center. G.S. Abdellrazeq and H.M. Rihan were supported by fellowships from the Egyptian Educational Bureau.
- Animal model
- Crohn's disease
- Flow cytometry
- Johne's disease
- Mycobacterium avium subsp. paratuberculosis