Modeling tuberculosis pathogenesis through ex vivo lung tissue infection.

Area of Science:

• Immunology
• Pathology
• Microbiology

Background:

• Tuberculosis (TB) remains a leading global cause of mortality.
• Existing in vitro and in vivo models have limitations in replicating the complex lung environment during Mycobacterium tuberculosis infection.

Purpose of the Study:

• To introduce and validate Precision Cut Lung Tissue Slices (PCLTS) as a novel experimental model for studying Mycobacterium tuberculosis infection.
• To assess the utility of PCLTS in examining early host-pathogen interactions and immune responses.

Main Methods:

• Precision Cut Lung Tissue Slices (PCLTS) were prepared and maintained in physiological conditions, verified by MTT assay and histology.
• PCLTS were infected with virulent Mycobacterium tuberculosis (H37Rv) or Mycobacterium bovis BCG strains.
• Histological analysis and TNF-α measurement were performed to evaluate infection and immune response.

Main Results:

• Histological examination revealed Mycobacterium tuberculosis localization within alveolar septa, air spaces, near type II pneumocytes, and within macrophages in PCLTS.
• Mycobacterial infection of PCLTS successfully induced the production of TNF-α, a key inflammatory cytokine.
• The PCLTS model maintained tissue architecture and cellular interactions, crucial for studying organ-specific responses.

Conclusions:

• Precision Cut Lung Tissue Slices (PCLTS) represent a viable and informative model for investigating Mycobacterium tuberculosis infection.
• This model facilitates the study of early innate immune responses and pathogen behavior in a physiologically relevant lung microenvironment.
• PCLTS offer a valuable tool for TB research, bridging the gap between traditional in vitro and in vivo methods.