Inflammatory Macrophages Associate With Tissue Injury and Fibrosis in a Mouse Model of Tuberculosis

Area of Science:

• Pulmonary Medicine
• Immunology
• Pathology

Background:

• Post-tuberculosis lung disease (PTLD) is a significant global health issue.
• Pathologic features like cavitation, bronchiectasis, and fibrosis characterize PTLD.
• Molecular mechanisms driving PTLD pathogenesis remain largely unknown.

Purpose of the Study:

• To investigate the molecular mechanisms underlying PTLD.
• To study TB-associated pathologic tissue remodeling and fibrosis using a mouse model.
• To compare fibrosis morphology in mouse models with human tissue samples.

Main Methods:

• Adaptation of a mouse model for tuberculosis (TB) infection.
• Second Harmonic Generation microscopy to assess fibrillar collagen deposition.
• Analysis of inflammatory transcriptional signatures and macrophage populations.
• Immunofluorescence microscopy to examine cell populations at fibrotic sites.

Main Results:

• Mouse model fibrosis morphology mimicked human PTLD.
• Fibrillar collagen deposition persisted despite anti-TB antibiotic treatment.
• Persistent inflammatory transcriptional signatures and macrophage populations were observed.
• Type 2 alveolar cells showed altered abundance and distribution at fibrotic sites.

Conclusions:

• PTLD-associated fibrosis and inflammation may not resolve with standard anti-TB therapy.
• Persistent macrophages and altered alveolar cell distribution contribute to fibrogenesis in PTLD.
• The mouse model provides a platform for studying PTLD mechanisms.