Figure 1

A model for granuloma dynamics of bovine paratuberculosis. MAP crosses the intestinal barrier via M cell or enterocyte transcytosis (1) and is subsequently taken up by macrophages in a predominantly tolerizing (2a) or a pro-inflammatory (2b) lamina propria compartment, the state of which may be determined by interplay between different dendritic cells (DC) subsets and enterocytes in combination with antigens present at that particular time. Subsequently the granuloma will develop into a pluribacillary (2a) or a paucibacillary (2b) lesion respectively. Depending on reaching bursting capacity due to bacterial replication (3a) or the end of the natural lifespan of macrophages or non-MAP related causes of cell death (3b) the infected macrophages will die and release MAP and MAP antigens into the lamina propria. Free MAP will enter the intestinal lumen via fluid streams and/or will be taken up by macrophages and DC migrating to the lumen thus leading to shedding of MAP in feces (4). Cellular debris and free MAP antigens from the lesion will be cleared and lead to the formation of scar tissue characterized by multinucleated giant cells and essential devoid of MAP. MAP and MAP antigen taken up by phagocytozing cells residing in the lamina propria may spread to different sites in the intestine and restart formation of a lesion or enter the afferent lymph (6) and migrate to the draining lymph node causing lymph node lesions or activation of T and B cells when taken up and properly processed by antigen presenting cells either on route or in the lymph node (7). Activated T cells and B cell derived antibodies as well as monocytes will enter the intestine via the arterio-venous capillary bed (8).