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.