Toll-like receptors blocking restores in vitro microbicidal activity in latent tuberculosis-infected subjects

Background Latent tuberculous infection (LTBI) can function as a 'reservoir' for Mycobacterium tuberculosis . Given that T-regulatory cell (T reg ) numbers are augmented in LTBI, it is likely that Toll-like receptors (TLRs) may have a role in T reg function. Elucidation of the immune mechanisms associated with tuberculosis (TB) development may help to control M. tuberculosis spread . OBJECTIVE: To investigate the role of TLR2, TLR4 and TLR9 in hindered in vitro microbicidal activity and increase T reg number during LTBI. Design Whole blood cell cultures from individuals with LTBI and healthy controls (HCs) infected with live M. tuberculosis H37Rv strain were used to investigate the effect of TLR2, TLR4 and TLR9 on T reg number, microbicidal activity, and interferon-gamma and interleukin (IL)10 production. Results LTBI subjects were characterised by increased T reg number and impaired microbicidal activity when compared with HCs. Specific blockade of TLR4 and TLR9 led to a significant reduction in T reg number, a decrease in IL-10 production and substantial upregulation of microbicidal activity. Conclusion M. tuberculosis infection may activate TLR4 and TLR9 pathways to suppress M. tuberculosis- specific immune responses. Here, we show that activation of TLR4 and TLR9 hinder microbicidal activity during LTBI.