A 3D Organotypic Human Bronchial Model Reveals Persistent Infection and Modulated Inflammatory Response when Exposed...

Area of Science:

• Microbiology
• Immunology
• Respiratory Medicine

Background:

• Brucella infection is often inhaled but its interaction with airways is poorly understood.
• The systemic dissemination of Brucella from the lungs highlights a knowledge gap in airway pathogenesis.

Purpose of the Study:

• To investigate Brucella abortus interaction with human bronchial tissues.
• To analyze bacterial replication, translocation, and host cytokine responses in a 3D airway model.

Main Methods:

• Utilized a 3D air-exposed organotypic human bronchial tissue model.
• Inoculated with Brucella abortus and monitored bacterial persistence, cytotoxicity, and cytokine release over 16 days.
• Compared Brucella with Escherichia coli and analyzed cell monocultures for immune cross-talk.

Main Results:

• Brucella abortus successfully invaded, replicated, and persisted in bronchial tissue without causing cytotoxicity.
• Viable bacteria were released from the basolateral side of the bronchial tissue.
• Increased levels of IL-6, IL-8, and MCP-1 were observed, along with elevated collagenase/gelatinase activity.
• Demonstrated infection transference and immune cross-talk between bronchial epithelial cells and lung fibroblasts.

Conclusions:

• The bronchial mucosa supports Brucella abortus persistence, replication, and dissemination.
• Brucella infection induces a proinflammatory response involving both epithelial and fibroblast cells.
• The study elucidates the role of the airway mucosa in early Brucella pathogenesis and host response.