The interaction of B. pertussis with human macrophages
B. pertussis was historically described as an extracellular pathogen, which, in the presence of specific antibodies, can be internalized and killed by phagocytic cells. Nevertheless, some reports suggested that in the absence of opsonization, this pathogen stimulates its own attachment to immune cells resulting in inefficient killing by phagocytes and increased intracellular survival. These data led to speculations that B. pertussis can use macrophages as an intracellular niche and that the intramacrophage phase of infection could play a significant role in survival and persistence of bacteria within the host. To gain insight into Bordetella-macrophage interplay we used RNA sequencing to analyze the changes in gene expression profiles of human THP-1 macrophages resulting from B. pertussis infection. In parallel, we attempted to determine the changes in transcriptomic profiles of intracellular bacteria resulting from interaction with macrophages.
Our analysis revealed that global gene expression profiles in THP-1 macrophages are extensively rewired 6 h post infection. Among the highly expressed genes we identified those encoding cytokines, chemokines and transcription regulators involved in the induction of the M1 and M2 macrophage polarization programs. Notably, several host genes involved in the control of apoptosis and inflammation which are known to be hijacked by intracellular bacterial pathogens were overexpressed upon infection. Furthermore, in silico analyses identified large temporal changes in expression of specific gene subsets involved in signaling and metabolic pathways. Our dual RNA-seq analysis revealed that B. pertussis cells actively adapt to intramacrophage environment and respond to bactericidal activities triggered by THP-1 cells. Our results suggest that intracellular B. pertussis cells have adopted avirulent phenotype to acclimate to the intramacrophage environment and we hypothesize that the avirulent phase represents an authentic phenotype of internalized B. pertussis cells.