Rapid and transient activation of gene expression in peripheral blood mononuclear cells from Johne's disease positive cows exposed to Mycobacterium paratuberculosis in vitro

Abstract

Mycobacterium avium subspecies paratuberculosis (M. paratuberculosis) is the causative agent of Johne's disease in ruminants. M. paratuberculosis is a slow-growing intracellular bacterium and infections with M. paratuberculosis can persist in a subclinical state for several years. An early and appropriate T cell-mediated cytotoxic response (Th1-like) to M. paratuberculosis infection is often replaced with an antibody or Th 2-like response as infected animals move toward a progressively more clinical state. The reasons for this shift in immune response are unknown. Recent studies suggest that in vitro exposure of peripheral blood mononuclear cells (PBMCs) from Johne's disease positive cows to M. paratuberculosis for 18-24 h results in suppressed expression of numerous immune cell genes. This effect appears at odds with the notion that immune cells from infected cows would respond to M. paratuberculosis-specific antigens in a vigorous and positive manner. In this report, we detail experiments designed to test the hypothesis that many positive changes in PBMC gene expression induced by M. paratuberculosis in vitro are transient, being rapidly suppressed by as yet unknown mechanisms. Our results demonstrate that, indeed, in vitro stimulation with M. paratuberculosis induces rapid changes in infected cow PBMC gene expression (within 2-4 h of exposure) and that many of these changes are no longer evident by 8-16 h of exposure to M. paratuberculosis. Although precise mechanisms responsible for rapid M. paratuberculosis-mediated activation of PBMC gene expression and the loss thereof remain to be determined, our novel results suggest that PBMCs from Johne's disease positive cows are indeed capable of vigorously responding to M. paratuberculosis and that, for many genes, this response is tempered within 8 h of exposure.