Host-directed therapy to combat mycobacterial infections

Area of Science:

• Infectious Diseases
• Immunology
• Microbiology

Background:

• Mycobacterium tuberculosis (Mtb) and nontuberculous mycobacteria (NTM) employ sophisticated strategies to evade host immune defenses and establish persistent infections.
• Pathogenic mycobacteria manipulate host cellular processes such as phagosome maturation, vacuolar escape, autophagy, antigen presentation, and metabolism to ensure survival.
• Conventional antibiotics face challenges with drug resistance and dormant bacterial forms, necessitating alternative treatment approaches.

Purpose of the Study:

• To review host-pathogen interactions identified for Mtb infections and explore potential host-directed therapeutic (HDT) strategies targeting innate and adaptive immunity.
• To discuss the potential application of HDTs for nontuberculous mycobacteria (NTM) infections, acknowledging current knowledge gaps.
• To highlight HDT strategies that warrant further research for improved mycobacterial infection control.

Main Methods:

• Literature review focusing on host-pathogen interactions in mycobacterial infections, particularly Mtb.
• Analysis of identified host-pathogen interaction mechanisms amenable to therapeutic intervention.
• Exploration of existing and potential HDT strategies impacting host immunity against mycobacteria.

Main Results:

• HDTs present significant advantages over conventional antibiotics, including efficacy against drug-resistant and dormant mycobacteria, reduced risk of inducing resistance, and potential for synergistic or shortened treatment regimens.
• Several HDT targets impacting both innate and adaptive immunity have been identified for Mtb infections.
• Knowledge regarding host-pathogen interactions for NTM is less developed compared to Mtb, indicating a need for further research.

Conclusions:

• Host-directed therapies (HDTs) represent a viable and advantageous therapeutic avenue for combating mycobacterial infections, including those caused by Mtb and NTM.
• Targeting host immune mechanisms offers a complementary strategy to conventional antibiotics, potentially overcoming resistance and improving treatment outcomes.
• Combinatorial HDT strategies hold promise for achieving optimal host immune control over mycobacterial infections, warranting extensive future investigation.