Generating Three-dimensional Human Granulomas in vitro to Study Mycobacterium tuberculosis-Host Interaction

Area of Science:

• Immunology
• Microbiology
• Infectious Diseases

Background:

• Granulomas are key structures in Mycobacterium tuberculosis (Mtb) infections.
• Understanding host-Mtb interactions within granulomas is crucial for developing new tuberculosis (TB) therapies.
• Existing in vitro models have limitations in fully recapitulating granuloma complexity.

Purpose of the Study:

• To develop a novel 3D in vitro model of human granulomas.
• To enable detailed analysis of host-Mtb interactions within a physiological matrix.
• To capture Mtb dormancy and resuscitation dynamics.

Main Methods:

• Embedding Mtb-infected human peripheral blood mononuclear cells (PBMCs) in a collagen matrix.
• Formation of three-dimensional micro-granulomas.
• Retrieval of PBMCs and Mtb for multiparametric analysis.

Main Results:

• Successful formation of 3D micro-granulomas recapitulating key features of human granulomas.
• The model supports dormant-like Mtb states.
• Mtb resuscitation under immunomodulatory treatments was observed, a novel finding for in vitro models.

Conclusions:

• The developed 3D micro-granuloma model provides a valuable tool for studying host-Mtb interactions.
• This model advances in vitro tuberculosis research by incorporating physiological matrices and Mtb dormancy/resuscitation dynamics.
• It holds potential for identifying new therapeutic and preventive strategies against tuberculosis.