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Updated: Jun 23, 2025
A 3D Human Lung Tissue Model for Functional Studies on Mycobacterium tuberculosis Infection
Published on: October 5, 2015
A mouse model of TB-associated lung fibrosis reveals persistent inflammatory macrophage populations during treatment
Julie Boucau1, Threnesan Naidoo2,3, Yuming Liu4
1The Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, USA.
Abstract:
Post-TB lung disease (PTLD) causes a significant burden of global disease. Fibrosis is a central component of many clinical features of PTLD. To date, we have a limited understanding of the mechanisms of TB-associated fibrosis and how these mechanisms are similar to or dissimilar from other fibrotic lung pathologies. We have adapted a mouse model of TB infection to facilitate the mechanistic study of TB-associated lung fibrosis. We find that the morphologies of fibrosis that develop in the mouse model are similar to the morphologies of fibrosis observed in human tissue samples. Using Second Harmonic Generation (SHG) microscopy, we are able to quantify a major component of fibrosis, fibrillar collagen, over time and with treatment. Inflammatory macrophage subpopulations persist during treatment; matrix remodeling enzymes and inflammatory gene signatures remain elevated. Our mouse model suggests that there is a therapeutic window during which adjunctive therapies could change matrix remodeling or inflammatory drivers of tissue pathology to improve functional outcomes after treatment for TB infection.
Insights
Post-TB lung disease (PTLD) involves significant lung fibrosis. A new mouse model shows similar fibrosis to humans, identifying potential therapeutic windows for improving outcomes after TB treatment.
Area of Science:
- Pulmonology
- Immunology
- Pathology
Background:
- Post-tuberculosis lung disease (PTLD) presents a substantial global health challenge, with fibrosis being a key pathological feature.
- Understanding the mechanisms of TB-associated fibrosis and its relation to other fibrotic lung diseases is limited.
- Current knowledge gaps hinder the development of targeted therapies for PTLD.
Purpose of the Study:
- To adapt a mouse model for studying the mechanisms of TB-associated lung fibrosis.
- To investigate the similarities between fibrosis in the mouse model and human PTLD tissue.
- To explore potential therapeutic strategies by analyzing matrix remodeling and inflammation during PTLD.
Main Methods:
- Adaptation of a mouse model for studying tuberculosis (TB) infection and subsequent lung fibrosis.
- Utilizing Second Harmonic Generation (SHG) microscopy to quantify fibrillar collagen, a key component of fibrosis.
- Analysis of persistent inflammatory macrophage subpopulations and elevated matrix remodeling enzymes and inflammatory gene signatures during treatment.
Main Results:
- The developed mouse model exhibits fibrosis morphologies comparable to those observed in human PTLD tissue samples.
- SHG microscopy enabled quantitative assessment of fibrillar collagen changes over time and in response to treatment.
- Persistent inflammatory macrophages and elevated inflammatory/remodeling markers were observed even after treatment initiation.
Conclusions:
- The adapted mouse model effectively recapitulates key features of human TB-associated lung fibrosis.
- The findings suggest a therapeutic window exists during PTLD treatment for interventions targeting matrix remodeling and inflammation.
- Targeting these drivers may improve functional outcomes for patients with PTLD.
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