Host-directed therapeutics for tuberculosis: can we harness the host?

Area of Science:

• Microbiology
• Immunology
• Pharmacology

Background:

• Tuberculosis (TB) treatment is challenging due to long durations, complex drug regimens, and toxicity.
• Current anti-TB drugs target Mycobacterium tuberculosis, but a biological limit may necessitate new approaches.
• Host-pathogen interactions and host immunity research suggest host-directed interventions can improve TB therapy.

Purpose of the Study:

• To review molecular pathways in the host amenable to small molecule modulation for TB treatment.
• To identify host targets that can augment standard anti-TB therapy.
• To focus on host modulators acting within myeloid cells, inflammatory pathways, or on TB-induced lung pathology.

Main Methods:

• Literature review of host-directed interventions for TB.
• Identification of molecular targets within host cells (macrophages, myeloid cells).
• Analysis of host inflammatory pathways and TB-induced lung pathology.

Main Results:

• Several host-directed approaches are proposed, but few are advanced in preclinical or clinical studies.
• Focus on small molecules targeting host pathways offers potential for improved TB treatment.
• Host modulators may reduce treatment time, lung damage, and risk of relapse or reinfection.

Conclusions:

• Host-directed therapies represent a promising new strategy to overcome limitations of current TB treatment.
• Modulating host pathways, particularly within myeloid cells and inflammatory responses, could significantly improve TB outcomes.
• Further research and development of host-directed small molecules are crucial for advancing TB treatment.