Mycobacterium paratuberculosisand the bovine immune system

Abstract

AbstractMycobacterium aviumsubspeciesparatuberculosis(M. paratuberculosis) is the causative agent of Johne’s disease, a deadly intestinal ailment of ruminants. Johne’s disease is of tremendous economic importance to the worldwide dairy industry, causing major losses due to reduced production and early culling of animals. A highly controversial but developing link between exposure toM. paratuberculosisand human Crohn’s disease in some individuals has led to the suggestion thatM. paratuberculosisis also a potential food safety concern. As with many other mycobacteria,M. paratuberculosisis exquisitely adapted to survival in the host, despite aggressive immune reactions to these organisms. One hallmark of mycobacteria, includingM. paratuberculosis, is their propensity to infect macrophages. Inside the macrophage,M. paratuberculosisinterferes with the maturation of the phagosome by an unknown mechanism, thereby evading the host’s normal first line of defense against bacterial pathogens. The host immune system begins a series of attacks againstM. paratuberculosis-infected macrophages, including the rapid deployment of activated γδ T cells, CD4+T cells and cytolytic CD8+T cells. These cells interact with the persistently infected macrophage and with each other through a complex network of cytokines and receptors. Despite these aggressive efforts to clear the infection,M. paratuberculosispersists and the constant struggle of the immune system leads to pronounced damage to the intestinal epithelial cells. Enhancing our ability to control this important and tenacious pathogen will require a deeper understanding of howM. paratuberculosisinterferes with macrophage action, the cell types involved in the immune response, the cytokines these cells use to communicate, and the host genetic factors that control the response to infection.