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ARS Home » Midwest Area » Ames, Iowa » National Animal Disease Center » Infectious Bacterial Diseases Research » Research » Publications at this Location » Publication #326113
Title: Divergent cellular responses during asymptomatic subclinical and clinical states of disease in cows naturally infected with Mycobacterium avium subsp. paratuberculosis

Author
item Stabel, Judith
item Bannantine, John

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 3/18/2016
Publication Date: 6/9/2016
Citation: Stabel, J.R., Bannantine, J.P. 2016. Divergent cellular responses during asymptomatic subclinical and clinical states of disease in cows naturally infected with Mycobacterium avium subsp. paratuberculosis. Meeting Abstract. Stabel, Judith R., Bannantine, John. P. 2016. 13th International Colloquium on Paratuberculosis. Page 40.

Interpretive Summary:

Technical Abstract: Infection of the host with Mycobacterium avium subsp. paratuberculosis (MAP) results in a chronic and progressive enteritis that traverses both subclinical and clinical stages. The mechanism(s) for the shift from asymptomatic subclinical disease state to advanced clinical disease are not fully understood but host immunity is decidedly a factor. Th1-mediated immunity dominates the early subclinical stage of infection with Th2 dominated immunity observed during clinical disease. However, this paradigm is an oversimplification as significant overlap of Th1/Th2 immunity exist in infected animals, even those that are eventually culled because of advanced clinical disease. More recently, CD4plus Th17-mediated immunity has been proposed as a significant immune mediator in mycobacterial infections. In the present study, naturally infected dairy cattle were defined as either subclinical and clinical infection groups, along with noninfected control cows of similar parity to study host immune responses in different stages of infection. Percentages of CD4plus and CD8plus T cells within freshly isolated PBMCs were lower in cows with clinical disease compared to subclinical cows. Interestingly, although the percentage of gamma delta TCRplus T cells was also reduced in total PBMCs from clinical cows, antigen stimulation of cells provoked an increase in activation markers on this cell subset. Both infection groups had higher secretion of IFN-gamma, TNF-alpha, and IL-2, whereas only clinical cows had increased secretion of IL-10, IL-12 and IL-18 upon stimulation of cells with antigen. Conversely, secretion of IL-17alpha was decreased for clinical cows. The majority of differences in cytokine gene expression between subclinical and clinical disease states were increased IFN-gamma, IL-12, IL-18, RANTES, IL-23, and iNOS, as well as IL-4 noted for subclinical cows. Increased IL-10 and IL-17 gene expression were observed for both infection groups compared to the control noninfected cows. We reason that a complex coordination of immune responses occurs during MAP infection, with these responses shifting as the host transitions through the different stages of infection and disease (subclinical to clinical). Further understanding of this series of events as characterized by Th1/Th2/Th17 responses will provide knowledge of Johne’s Disease progression and may direct insightful intervention strategies.