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Title:   Author  item
                                            Palmer, Mitchellitem
                                            Thacker, Tyleritem
                                            Waters, Wade
  Submitted to: Veterinary Immunology and Immunopathology
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 8/31/2016
                                    Publication  Date: 9/10/2016
                                    Citation: Palmer, M.V., Thacker, T.C., Waters, W.R. 2016. Multinucleated giant cell cytokine expression in pulmonary granulomas of cattle experimentally infected with Mycobacterium bovis. Veterinary Immunology and Immunopathology. 180:34-39.Interpretive Summary: The bacterium Mycobacterium bovis is the cause of tuberculosis in most animal species and humans. Tuberculosis disease is manifested by formation of granulomas within the lungs. In the present study it was shown that specific cells within granulomas produce various inflammatory mediators and that in some cases, and not others, this expression changes as the granuloma develops. Knowing what cells compose granulomas and their functions will aid in development of diagnostic tests and effective vaccines.
                                Technical Abstract: Pathogenic mycobacteria of the Mycobacterium tuberculosis complex such as Mycobacterium bovis, induce a characteristic lesion known as a granulomas. Granulomas represent a specific host response to chronic antigenic stimuli, such as foreign bodies, certain bacterial components, or persistent pathogens such as M. bovis. Granulomas are composed of specific cell types including epithelioid macrophages and a morphologically distinctive cell type, the multinucleated giant cell. Multinucleated giant cell function remains unclear. In humans, giant cells in tuberculous lesions have been shown to express various cytokines, chemokines and enzymes important to the formation and maintenance of the granuloma. Using calves experimentally infected with M. bovis and examined 150 days later, in situ cytokine expression was quantitatively examined using RNAScope® for the following cytokines TNF-alpha, IFN-gamma, TGF-beta, IL-17A and IL-10. Multinuceated giant cells in bovine tuberculoid granulomas expressed all cytokines examined to varying degrees, with differential expression of TGF-beta, IL-17A and IL-10 in early versus late stage granulomas. There was a modest, positive correlation between the level of cytokine expression and cell size or number of nuclei. Multinucleated giant cells are not only morphological distinct cells, but also active participants within granulomas, contributing to the cytokine milieu necessary to form and maintain granulomas.


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