Intracellular trafficking of Bordetella pertussis in human macrophages

Area of Science:

• Immunology
• Microbiology
• Cell Biology

Background:

• Bordetella pertussis, the causative agent of whooping cough, survives within host macrophages.
• The intracellular survival mechanisms of B. pertussis, particularly its evasion of phagolysosomal degradation, remain incompletely understood.

Purpose of the Study:

• To investigate the intracellular trafficking and survival mechanisms of Bordetella pertussis within human macrophages.
• To determine the specific host cell compartments utilized by B. pertussis for survival and replication.

Main Methods:

• Phagocytosis assays using human macrophages and B. pertussis.
• Immunofluorescence microscopy to track bacterial location relative to endosomal/lysosomal markers (LAMP, Rab5).
• Assessment of bacterial viability and replication over time post-infection.
• Transferrin uptake assays to evaluate nutrient acquisition.

Main Results:

• A significant portion of B. pertussis is initially killed in acidic, LAMP-positive compartments (lysosomes).
• Approximately 25% of ingested bacteria evade initial killing and survive in nonacidic compartments.
• Intracellular B. pertussis replicates within 48 hours, accumulating in Rab5-positive early endosomes, not LAMP-positive late endosomes.
• B. pertussis-containing phagosomes acquire transferrin, indicating access to extracellular nutrients.

Conclusions:

• Bordetella pertussis survives and replicates within human macrophages by exploiting early endosomal compartments.
• This intracellular survival strategy, involving nutrient acquisition via host cell pathways, likely contributes to B. pertussis persistence.
• Understanding these mechanisms is crucial for developing strategies to combat whooping cough and its spread.