Floating between the poles of pathology and protection: can we pin down the granuloma in tuberculosis?

The granuloma in tuberculosis (TB), referred to as the tubercle, is a lesion containing multiple cell types and is the one definite hallmark of this disease. A number of tubercle phenotypes are seen during infection yet how these contribute to development of TB remains unclear. Here we highlight recent results using diverse models of tubercle development as well as recent findings from studies of human TB in an attempt to illustrate the plasticity of the tubercle and to place it between the poles of pathology and protection. Such insights could lead to future interventions to address TB as a global health issue.

► Granuloma (tubercle) in protection and pathogenesis of TB is appreciated. ► Tubercle shows high plasticity with a continuum of solid, necrotic and caseous forms. ► Mechanisms underlying the role of tubercles in TB protection/pathogenesis remain elusive. ► Cytokines, IL-12, IL-17, IFN-γ, TNF and many chemokines are crucial for granuloma formation. ► Leukotriene B4 and metalloproteineases are crucial for tubercle maturation.