Citation: Khalifeh, M.S., Stabel, J.R. 2013. Clinical disease upregulates expression of CD40 and CD40 ligand on peripheral blood mononuclear cells from cattle naturally infected with Mycobacterium avium subsp. paratuberculosis. Clinical and Vaccine Immunology. 20(8):1274-1282.
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. Johne's disease is difficult to manage and control on-farm. This study evaluates the measurement of markers on the immune cells of infected and noninfected animals as a means of differentiating between the stages of disease. This information also helps us with understanding key markers 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: CD40 and CD40L interactions have costimulatory effects that are part of a complex series of events in host cellular and humoral immune responses and inflammation. The purpose of this study was to examine the changes in expression of CD40 and CD40L on peripheral blood mononuclear cells (PBMCs) isolated from cattle with Johne's disease. CD40 and CD40L were measured on freshly isolated PBMCs and after culture of cells for 8, 24, and 72 hr in the presence or absence of live Mycobacterium avium subsp. paratuberculosis (MAP). Results demonstrated greater CD40 and CD40L expression on fresh PBMCs obtained from animals in the clinical stage of disease (symptomatic) compared to healthy controls and asymptomatic cows in the subclinical stage of disease. A similar expression profile was noted, but with a higher magnitude, after culture of PBMCs with increases in CD40 expression after 8 and 24 hr of culture and in CD40L expression between 24 and 72 hr on PBMCs obtained from clinical animals. Addition of live MAP to cell cultures resulted in downregulation in CD40L expression in naturally infected cows, regardless of the disease stage. In contrast, adding live MAP to cultures resulted in an upregulation of CD40 expression on cells obtained from clinically infected animals while a decrease in expression was noted for healthy and subclinically infected cows. These results clearly point for the first time to a disparity in the expression of these costimulatory molecules on immune cells from cattle in different stages of Johne's disease and provoke further investigation into their role in paratuberculosis pathogenesis.