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An Automated Culture System for Use in Preclinical Testing of Host-Directed Therapies for Tuberculosis
Published on: August 16, 2021
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Host-directed therapies targeting the tuberculosis granuloma stroma
Elinor Hortle1,2, Stefan H Oehlers1,2
1Tuberculosis Research Program at the Centenary Institute, The University of Sydney, Camperdown, NSW 2050, Australia.
Pathogens and Disease
|March 10, 2020
Summary
Host-directed therapies (HDTs) target granuloma stroma to combat mycobacterial infections. Relieving stromal pathologies offers a novel strategy for treating tuberculosis by enhancing host immunity.
Area of Science:
- Immunology
- Microbiology
- Pathology
Background:
- Pathogenic mycobacteria excel at intracellular survival within macrophages.
- Granulomas form as a host response but create niches that promote pathogen survival and antibiotic resistance.
- Current treatments often struggle against mycobacteria residing within granulomas.
Purpose of the Study:
- To review innovative research on host-directed therapies (HDTs) for mycobacterial infections.
- To highlight the role of granuloma stroma as a primary driver of infection.
- To summarize advances in targeting host vasculature, hemostasis, and extracellular matrix.
Main Methods:
- Review of preclinical and clinical studies on HDTs.
- Analysis of research on host-pathogen interactions within granulomas.
- Exploration of host-pathogen co-evolutionary dynamics.
Main Results:
- 'Secondary' symptoms in the granuloma stroma are identified as primary drivers of infection.
- Relieving stromal pathologies with HDTs benefits the host by restoring immunity.
- HDTs offer a strategy independent of pathogen antimicrobial resistance.
Conclusions:
- Targeting granuloma stromal pathologies represents a promising host-directed approach.
- Understanding host-pathogen interactions in the stroma is crucial for developing effective HDTs.
- HDTs against stromal targets show potential in preclinical and clinical settings for tuberculosis treatment.
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