Mycobacterium avium subsp. paratuberculosis (M. a. paratuberculosis) is the cause of paratuberculosis, which is a chronic enteritis of ruminants characterized by granulomatous inflammation. The transmission of the infection is mainly by faecal contaminated feed. The bacteria are transported from the intestinal lumen into the intestinal wall via M cells, which overlie the domes of Peyer's patches. It is proposed that integrin receptors on the apical surface of M cells bind fibronectin-opsonized bacteria, facilitating phagocytosis by these cells. After crossing the epithelial barrier of the intestine, the bacteria are phagocytosed by macrophages, which are the target cell for this microorganism. Macrophages internalize the bacteria by binding to different receptors, including the complement receptor 3, and phagosomes containing the organisms are formed. Macrophages can destroy M. a. paratuberculosis, but not by way of oxidative compounds. The bacteria manipulate macrophages in order to survive, inhibiting the maturation and acidification of the phagosomes, and modulating macrophage cytokine production and antigen-presentation.