Relationship between the pathology of bovine intestinal tissue and current diagnostic tests for Johne's disease

Authors: JENVEY, CAITLIN - US Department Of Agriculture (USDA); HOSTETTER, J - Iowa State University; Shircliff, Adrienne; Stabel, Judith

Submitted to: Veterinary Immunology and Immunopathology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/18/2018
Publication Date: 6/23/2018
Citation: Jenvey, C.J., Hostetter, J.M., Shircliff, A.L., Bannantine, J.P., Stabel, J.R. 2018. Relationship between the pathology of bovine intestinal tissue and current diagnostic tests for Johne's disease. Veterinary Immunology and Immunopathology. 202:93-101. https://doi.org/10.1016/j.vetimm.2018.06.012.
DOI: https://doi.org/10.1016/j.vetimm.2018.06.012

Interpretive Summary: Confocal microscopy is a widely used method utilizing fluorescence to identify the presence of cell types within tissues and/or bacterial or viral pathogens. This method has been used successfully to detect the presence of bacterial pathogens such as mycobacteria and to correlate that presence with the pathogenesis of disease. Understanding the pathogenesis of disease and the host immune response to infection will allow us to develop improved diagnostic tools and vaccines. In the present study, mid-ileal tissue from naturally infected cattle was stained for macrophage and Mycobacterium avium subsp. paratuberculosis (MAP) and visualized by confocal microscopy. Quantitative staining of the tissues was correlated with current diagnostic tests for Johne’s disease. The test with the highest correlation to tissue pathogenesis was the serum ELISA test that measures serum antibodies to MAP. The models developed for this analysis were useful in assessing the utility of current diagnostic tests to predict clinical disease in cattle, something that will be helpful to producers that may need to consider culling of infected animals from the herd.

Technical Abstract: Johne’s disease is an enteric disease caused by the intracellular pathogen Mycobacterium avium subsp. paratuberculosis (MAP). Upon translocation from the lumen of the small intestine, mycobacteria have the ability to thwart innate defense mechanisms and persist within the macrophage in the lamina propria. In an effort to understand how the pathology of disease is reflected in current diagnostic tests, immunofluorescent (IFA) labeling was performed to quantitate macrophage and MAP numbers in the ileum of infected cattle and correlate results with common methods for diagnosis of MAP infection; including ELISA, IFN-' assay, RT-PCR, culture of MAP, and histological classification of tissue sections. Predictive models for clinical and subclinical disease states, histopathology acid-fast (AF), MAP location, granulomatous inflammation and type classifications, as well as macrophage, MAP and macrophages with intracellular MAP IFA labeling were successfully developed. The combination of macrophage number and ELISA were the best predictors of clinical disease state, while macrophage number was the best and only significant predictor of subclinical disease state. Fecal culture and number of MAP were the best predictors of granulomatous inflammation, and of combined AF, MAP location and granuloma type, respectively. Additionally, fecal culture and tissue culture were the best predictors of numbers of macrophages and MAP, respectively, while both ELISA and tissue culture were the best predictors of number of macrophages with intracellular MAP.