Mycobacterial Factors Responsible for Granuloma Formation
Given the central importance of granuloma formation in tuberculosis, it would be assumed that the cell surface or secreted components of M. tuberculosis responsible for controlling the dynamic composition of the tuberculoid granuloma would be well established. Surprisingly, this is not the case. The cell-wall glycolipid, trehalose-6,6-dimycolate (TDM), also known as cord factor, was the first mycobacterial component to be shown capable of inducing granuloma formation (Yarkoni and Rapp 1977). There is also limited evidence from an in vitro human granuloma assay that proinflammatory lipoarabinomannans from M. tuberculosis can induce granuloma formation (Puissegur et al. 2007). Other key mycobacterial virulence factors such as lipoproteins, ESAT-6 (early secreted antigenic target-6), and CFP-10 (culture filtrate protein-10) (Xu et al. 2007) have major effects on myeloid cells, but have not been shown to be involved in granuloma formation. In contrast, there is emerging evidence that another virulence protein of M. tuberculosis - HSP65/chaperonin 60 - has a role to play in granuloma formation.
Figure 5.1 A cartoon view of the tuberculoid granuloma with cellular compositions deemed to be associated with bactericidal action or favoring bacterial persistence. Source: Lugo-Villarino et al. (2013).