Divergent antigen-specific cellular immune responses during asymptomatic subclinical and clinical states of disease in cows naturally infected with Mycobacterium avium subsp. paratuberculosis

Authors: Stabel, Judith; Bannantine, John

Submitted to: Infection and Immunity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/4/2019
Publication Date: 12/17/2019
Citation: Stabel, J.R., Bannantine, J.P. 2019. Divergent antigen-specific cellular immune responses during asymptomatic subclinical and clinical states of disease in cows naturally infected with Mycobacterium avium subsp. paratuberculosis. Infection and Immunity. 88(1):e00650-19. https://doi.org/10.1128/IAI.00650-19.
DOI: https://doi.org/10.1128/IAI.00650-19

Interpretive Summary: Johne's disease is a chronic, debilitating intestinal disorder in cattle characterized by diarrhea, reduced feed intake, weight loss and death. Cattle usually become infected as young calves by ingesting feces containing the causative bacteria. However, symptoms of disease do not usually present themselves until the animals reach 3 to 5 years of age or even older. During this time the animal is infected and may be shedding the organism in its feces without showing any clinical signs of disease. In addition to reduced milk production by these animals, they also present a potential infective threat to the rest of the herd. Little is known how the cow controls this infection in the early stages and what happens to allow full-blown disease to develop. This study presents information on measurements on immune cells from cows in different stages of disease and how these differ between the stages of disease. This information helps us with understanding key events in the progression of disease from the early asymptomatic stage to more advanced clinical disease. Understanding the host immune response to this pathogen will help us develop new therapeutic strategies as well as new diagnostic tools and vaccines to prevent the spread of disease.

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. 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. Both infection groups had higher secretion of IFN-g, TNF-a, and IL-2 than control cows, whereas only clinical cows had increased secretion of IL-10, IL-12, and IL-18 upon stimulation of PBMCs with antigen. Conversely, secretion of IL-17A was decreased for clinical cows compared to subclinical and control cows and aligned with decreased percentage of gd TCR+ T cells in total PBMCs from clinical cows. Increased IL-10 and IL-17 gene expression were observed for both infection groups compared to the control noninfected cows, whereas pro-inflammatory cytokine genes were upregulated only for subclinical 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 the series of events characterized by Th1/Th2/Th17 responses will provide mechanisms for disease progression and may direct insightful intervention strategies.