Submitted to: Veterinary Immunology and Immunopathology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/6/2004
Publication Date: 5/1/2004
Citation: Khalifeh, M.S., Stabel, J.R. 2004. Upregulation of transforming growth factor-beta and inteleukin-10 in cows with clinical johne's disease. Veterinary Immunology and Immunopathology. 99(1-2):39-46. Interpretive Summary: Johne's disease is a chronic, debilitating intestinal disorder in cattle characterized by diarrhea, reduced feed intake, weight loss and death. Cattle usually become infected as young calves by ingesting feces containing the causative bacteria. However, symptoms of disease do not usually present themselves until the animals reach 3 to 5 years of age or even older. During this time the animal is infected and may be shedding the organism in its feces without showing any clinical signs of disease. In addition to reduced milk production by these animals, they also present a potential infective threat to the rest of the herd. Johne's disease is difficult to diagnose and therefore to control. Development of accurate and sensitive diagnostic tests is dependent upon understanding the immune responses of the host animal during infection. This study demonstrated that animals in different stages of infection with the same microorganism have very different immune responses with high levels of interferon-gamma in subclinical infection and high levels of IL-10 and TGF-beta in clinical stages of infection. This information is helpful in understanding the difference between an animal being able to control the infection and an animal that succumbs to clinical disease. It is possible that this information will lead to better understanding of the pathogenesis of disease and aid in new preventative and therapeutic regimes.
Technical Abstract: Johne's disease progresses through distinct stages including a protracted sub clinical stage in which the infection appears to be controlled; followed by a more acute stage in which the host animal demonstrates clinical signs such as diarrhea and weight loss. Little is known about the dynamics of the host immune response during these two phases of disease, however, it is possible that immune modulation in the early stages of disease may play an important role in disease progression. We hypothesized that the clinical stage of Johne's disease is mediated by the expression of cytokines such as transforming growth factor-beta (TGF- Beta) and interleukin-10 (IL-10) that may be accompanied by the downregulation of IFN-gamma gene expression. In the present study, tissue samples were collected from the ileum, ileocecal junction, ileocecal lymph node, and mesenteric lymph nodes of health, subclinically or clinically infected cows. The expression of TGF-Beta and IL-10 mRNA levels are higher in cows that have progressed to the clinical stage of disease compared to subclinically infected or health cows. In contrast, IFN-gamma gene expression was significantly higher in subclinically infected cows. These results suggest that a change in the balance of cytokines at the site of infection may contribute to the ability of the host to control Mycobacterium avium subsp. Paratuberculosis infection.