Understanding Mycobacterium tuberculosis host immune responses and identifying synergistic autophagy-inducing compounds as potential nanomedicines for tuberculosis treatment.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (M. tb), poses a significant global health challenge and is currently the most fatal disease resulting from a single infectious agent. The development of drug-resistant strains, thin antibiotic pipeline, and limitations of current treatment regimens necessitate the development and exploration of new anti-TB treatmnt options. Host-directed therapies (HDTs) have emerged as a promising treatment option, due to their ability to modulate the host's immune system and target cellular processes vital for the replication and pathogenesis of invading pathogens. The keen focus on homeostatic medicines as HDTs that particularly induce autophagy and the synergism between these autophagy-inducing compounds remains an untapped therapeutic reservoir. However, limitations of current drug-delivery methods have proven to be a significant challenge. The encapsulation of autophagy-inducing compounds in nano-formulations can facilitate potential targeted delivery, enhanced efficacy, bioavailability, and sustained drug release, thus potentially reducing treatment durations. Systematic searches across PubMed and Google Scholar databases were conducted with inclusion of 154 articles published between December 2004 to June 2026. This review therefore explores the synergistic activity of autophagy‑inducing compounds and how it can be leveraged to develop new nanomedicines as potential HDTs for the treatment of TB.