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Granulomas are the hallmark of  Mycobacterium tuberculosis  ( M.tb ) infection and thus sit at the center of tuberculosis (TB) immunopathogenesis. TB can result from either early progression of a primary granuloma during the infection process or reactivation of an established granuloma in a latently infected person. Granulomas are compact, organized aggregates of immune cells consisting of blood-derived infected and uninfected macrophages, foamy macrophages, epithelioid cells (uniquely differentiated macrophages), and multinucleated giant cells (Langerhans cells) surrounded by a ring of lymphocytes. The granuloma’s main function is to localize and contain  M.tb  while concentrating the immune response to a limited area. However, complete eradication does not occur since  M.tb  has its own strategies to persist within the granuloma and to reactivate and escape under certain conditions. Thus  M.tb -containing granulomas represent a unique battlefield for dictating both the host immune and bacterial response. The architecture, composition, function, and maintenance of granulomas are key aspects to study since they are expected to have a profound influence on  M.tb  physiology in this niche. Granulomas are not only present in mycobacterial infections; they can be found in many other infectious and non-infectious diseases and play a crucial role in immunity and disease. Here we review the models currently available to study the granulomatous response to  M.tb .

Modeling the Mycobacterium tuberculosis Granuloma – the Critical Battlefield in Host Immunity and Disease