Advanced granulomatous lesions in Mycobacterium bovis-infected cattle are associated with increased expression of type I procollagen, γδ (WC1⁺) T cells and CD 68⁺ cells

The pathognomonic characteristic of tuberculosis (TB) is the formation of a tuberculous granuloma. The objective of this study was to classify lymph node granulomas from experimentally infected calves into different histopathological stages and characterize them further by studying cell types and markers of fibrosis associated with each of the stages. Four stages of granuloma were identified and mRNA and protein expression for cell markers, cytokines and pro-fibrotic markers were studied by immunohistochemistry (IHC) and in-situ hybridization (ISH). In advanced stage granulomas, there was an increase in the expression of TGF-β, and of type I procollagen as demonstrated by IHC and ISH. As the granulomas advanced, there were fewer CD3⁺T cells and they tended to be more prominent towards the periphery of the lesions, with a steady increase in the number of CD68⁺ cells and γδ (WC1⁺) T cells. Granuloma classification and application of cell cytokine markers will assist in improving understanding of the pathogenesis of bovine TB and may help to identify the immunopathology of active disease versus contained or inactive disease. Such disease correlates may help to inform the development of improved diagnostic methods and support vaccine development programmes.