Molecular evasion of bovine macrophage activation by Mycobacterium avium subspecies paratuberculosis

Mycobacterium avium subspecies paratuberculosis (MAP) is the causing agent of a chronic granulomatous disease affecting intestinal tract of domestic and wild ruminants known as Johne’s disease or paratuberculosis. MAP behaves as low growing mycobacteria in vitro. However, it can survive into the phagocytic vacuole of macrophages of a susceptible in vivo host. The infective capability of MAP depends on host susceptibility and they immune status at the time of infection and strain virulence of the mycobacteria. Once MAP is phagocytized by the bovine macrophage, specific profiles of gene transcription are produced into the bacteria, as well as within the macrophage genomes: MAP expresses genes related to survival into the phagolysosome that avoids its intracellular destruction and controls apoptosis of the infected macrophage, whereas macrophage expresses genes related to microbial processing and destruction within the phagocytic vacuole. The molecular events elicited by this encounter could drive the immune response of the host towards an efficient control of mycobacterial infection or towards the progression of the infection until establishment of Stages III (clinical intermittent) and IV (clinical terminal) of the disease. In this review we provide the reader with the basic concepts on the molecular mechanisms by which MAP can evade the host immune response, particularly on those processes related to its survival into the phagocytic vacuole that results in bacterial dissemination into the lymphoid system of a susceptible host.