Human TB granulomas may be non-necrotic or necrotic. Several different fates of granulomas occur and such heterogeneity may present in the same individual. (A) A non-necrotic TB granuloma is characterized by the presence of epithelioid macrophages and activated macrophages as well as fewer foamy macrophages, necrotic macrophages, neutrophils, and more or less a rim of host-protective T cells and B cells along with relatively few bacilli. iBALT may be considered an “appendage” of granulomas typically comprised of dendritic cells, B cells, and T cells and may serve as a ready supply of immune cells for the neighboring granuloma. This granuloma is protective as shown by the relatively few Mtb (red-colored rod-shaped structures. (B) A granuloma with central necrosis characterized by fewer epithelioid and activated macrophages and more foamy macrophages, necrotic macrophages, and neutrophils along with an area of central necrosis. There are also fewer host-protective T cells and B cells. Due to the fewer number of host-protective innate and adaptive immune cells, there is overall a greater Mtb burden. However, in the central necrotic area of this human granuloma, there is active killing of Mtb resulting in fewer viable Mtb in this region. Higher levels of MmpL7 and IDO-1 inhibit iBALT formation. IDO-1, indoleamine 2,3-dioxygenase; iBALT, inducible bronchus-associated lymphoid tissue; MmpL7, Mycobacterial membrane protein Large 7; Mtb, Mycobacterium tuberculosis; TB, tuberculosis.
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