Summary and future directions
It appears now from studies in animal models and humans that in TB the role of Tregs, both nTreg and antigen specific, has several dimensions. While Tregs might delay the appearance of protective Th responses especially during the early stages of infection; their function in the chronic stage of TB disease is consistent with their known primary function that is linked to control of exaggerated inflammation, which if unchecked, can contribute to disease pathology [116, 117]. The immune response in TB is clearly disordered and the theme of balance between protective and pathogenic responses has been visited in the past [118]. In fact, a balance between Th1/Th17 and immune-regulatory responses is associated with better clearance of Mtb infection [119]. In this context, the expansion of HLA-DR+Teff cells in TB is a likely marker for inflammation associated with enhanced disease risk [120]. It has now been demonstrated that this expanded subset exhibits resistance to suppression mediated by natural Treg cells [61]. The putative role of pro-inflammatory cytokines (IFNγ, IL-17A, IL-2, CSF2 and IL-22), β-chemokines and PD-1/PD-L1 interactions in modulating T effector resistance to Treg suppression in TB has been identified (Figure 2). This calls for further analysis of the mechanisms that are important in maintaining balance between inflammation and immune-regulation in TB.