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. 2019
Stabel JR and Bannantine JP
Infect Immun. 2019 Oct 14. pii: IAI.00650-19.
DOI doi: 10.1128/IAI.00650-19.
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 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-γ, TNF-α, 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. Pro-inflammatory cytokine genes were upregulated only for subclinical cows, whereas increased IL-10 and IL-17 gene expression were observed for both infection groups. Increased CD4+, CD8+ and γδ TCR+ T cells were observed for subclinical cows compared to clinical cows. Although clinical cows expressed antigen-specific immune responses, the profile for subclinical cows was one of a dominant pro-inflammatory response to infection. 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.