Host-Directed Therapeutics against Mycobacterial Infections

The high incidence of tuberculosis (TB) in the world, especially in developing countries, the resurgence of TB in industrialized countries, and the global increase in the prevalence of Mycobacterium avium complex infections in immunocompromised hosts have prompted the quest for novel antimycobacterial drugs. However, the development of such antimicrobial chemotherapeutics is currently making very slow progress even with using the bioinformatics-based methodology for drug design. It thus appears that devising improved administration protocols for clinical treatment against intractable mycobacterial infections using existing chemotherapeutics is more practical than awaiting the development of new antimycobacterial drugs. The potentiation of host immune responses using immunoadjunctive agents, alternatively called host-directed therapeutics (HDTs), may increase the efficacy of antimycobacterial regimens against mycobacteriosis. Particularly, the modulation of host immunity relating to macrophage antimicrobial functions may be beneficial to the immunoadjunctive therapy. This review will deal with the current status and future prospects regarding the development of HDTs useful for the clinical control of intractable mycobacterial infections.