Bordetella pertussis outer membrane vesicles impair neutrophil bactericidal activity

Abstract

Neutrophils constitute the primary defense against bacterial infections, yet certain pathogens express virulence factors that enable them to subvert neutrophils-mediated killing. Outer membrane vesicles (OMVs) have emerged as a secretory system through which bacteria deliver virulence factors to host cells. OMVs from Bordetella pertussis, the etiological agent of whooping cough, are loaded with most of bacterial virulence factors, including CyaA, which plays a key role in B. pertussis evasion of neutrophils bactericidal activity. In our study, we investigated the role of B. pertussis OMVs in bacterial interaction with neutrophils. We observed that interaction of OMVs with neutrophils led to a decrease in the expression of cell surface CR3 and FcγRs, an effect dependent on the CyaA toxin delivered by these vesicles. This decreased receptor expression led to reduced bacterial uptake by neutrophils, irrespective of the presence of opsonic antibodies. Moreover, CyaA delivered by OMVs hindered intracellular bactericidal trafficking, promoting bacterial intracellular survival. When both bacteria and OMVs were opsonized, competition between opsonized OMVs and B. pertussis for FcγRs on neutrophils led to a significant decrease in bacterial uptake. Overall, our findings suggest that B. pertussis OMVs promote bacterial survival to the encounter with neutrophils in both naïve and immunized individuals.