Fig. 1

Host-directed therapies aimed at modulating immune responses in the tuberculous lung. Overt immune responses characterise the pathological outcome in tuberculosis (TB). Neutralisation of pro-inflammatory cytokines such as IL-6, TNF-α, VEGF and IFN-αβ, as well as anti-inflammatory IL-4 during severe pulmonary disease may help reduce ongoing parenchymal damage in the lung. Alternatively, suboptimal activation of anti-TB immune responses due to regulatory T cell activity can be reversed by the use of the anti-cancer drug cyclophosphamide. Drugs with anti-TB potential, such as metformin, imatinib, ibuprofen, zileuton, valproic acid, and vorinostat as well as nutraceuticals such as vitamin D3 not only abate bacterial burden via host-dependent mechanisms, but may also fine-tune the immune response to Mycobacterium tuberculosis (M. tb). These drugs increase phagocytosis of extracellular bacteria, improved emergency myeloid response and increased autophagic and apoptotic killing of bacteria, subsequently editing the T cell response in favour of the host. Immune checkpoint inhibition with blockade of the PD-1/PD-L1, CTLA-4, LAG3 and TIM3 pathways may improve the quality of the cellular immune response to M. tb epitopes, as seen in cancer. A more complete list of currently pursued host-directed therapies for TB can be found in Table 1. Abbreviations: VPA, valproic acid; PBA, phenylbutyrate; PD-1, programmed cell death 1; PD-L1, PD-1 ligand 1; CTLA-4, cytotoxic T lymphocyte-associated antigen 4; LAG3, lymphocyte-activation gene 3; TIM3, T cell immunoglobulin and mucin domain 3