Phenotypes of macrophages present in the intestine are impacted by stage of diseae in cattle naturally infected with Mycobacterium avium subsp. paratuberculosis

Authors: JENVEY, C - US Department Of Agriculture (USDA); SHIRCLIFF, A - US Department Of Agriculture (USDA); Bannantine, John; Stabel, Judith

Submitted to: PLOS ONE
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/15/2019
Publication Date: 5/23/2019
Citation: Jenvey, C.J., Shircliff, A.L., Bannantine, J.P., Stabel, J.R. 2019. Phenotypes of macrophages present in the intestine are impacted by stage of disease in cattle naturally infected with Mycobacterium avium subsp. paratuberculosis. PLoS One. 14(5). https://doi.org/10.1371/journal.pone.0217649.
DOI: https://doi.org/10.1371/journal.pone.0217649

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 the 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. The type of macrophage present in the intestinal tissue of cows was differentiated by co-staining for other markers. Results demonstrated that there are different types of macrophages present in the tissues of cows that are asymptomatic compared to cows that had severe clinical disease. These results provide critical information on the biology of MAP infection within the target tissue and are useful for producers, clinicians and researchers to gauge the involvement of tissue during the different stages of disease.

Technical Abstract: Macrophages play an important role in the host immune response to Mycobacterium avium subsp. paratuberculosis (MAP) infection, however, MAP is able to disrupt normal macrophage functions to avoid destruction. It is unclear whether macrophage phenotypes may play a role in the inability of macrophages to clear MAP infection. The aim of this study was to identify macrophage phenotypes (host defense/resolution and repair) present within the bovine ileum of naturally infected cattle, as well as to identify relationships between the numbers of macrophage phenotypes present during different stages of MAP infection. Immunofluorescent (IF) labeling was performed on frozen bovine mid-ileal tissue section collected from 28 Holstein dairy cows. Clinical cows demonstrated significantly higher numbers of CD163+ and significantly lower numbers of CD206+ macrophages. Overall, clinical cows demonstrated significantly lower total numbers of macrophages with a host defense phenotype. Additionally, subclinical cows demonstrated an almost 1:1 ratio of host defense and resolution and repair phenotype macrophages, compared to dominant host defense and resolution and repair macrophage phenotypes in control and clinical cows, respectively. The results of the current study offer insight into macrophage phenotypes present in the bovine ileum during different stages of infection.