Targeting Inhibitory Cells Such as Tregs and MDSCs in the Tuberculous Granuloma

Mycobacterium tuberculosis (Mtb) is one of the most successful pathogenic agents infecting more than one-quarter of the human population and causing death of more than one million individuals in 2017 alone. The huge incidence rate, coupled with the emergence of multi- and extremely-drug resistant strains, raises the need for the development of novel therapeutic approaches that are more effective, less toxic, and require shorter treatment duration. As an alternative/adjuvant approach, host-directed therapies (HDTs) have come across as an attractive strategy that harnesses the host’s own immune potential to fight against bacterial infection. As an opportunistic pathogen, Mtb has the remarkable ability to suppress and modulate host immune responses that facilitate Mtb proliferation as well as its dissemination. This chapter highlights the role of two prominent immunosuppressive cell populations regulatory T-cells (Tregs) and myeloid-derived suppressor cells (MDSCs) in TB establishment, progression, dissemination, and formation of granulomas (the pathological hallmark of TB). The chapter also discusses various studies on therapeutics targeting of Tregs and MDSCs. The success of such studies holds promise for the development of HDTs as novel strategies for TB treatment.