Bordetella parapertussis Evades Neutrophil-Mediated Killing by Failing to Trigger Innate Activation Even After IFN-γ Priming.

B. parapertussis is one of the etiologic agents of whooping cough and its incidence has increased following the COVID-19 pandemic. Since current pertussis vaccines fail to induce protection against B. parapertussis, the course of infection critically relies on the innate immune response. However, in the absence of opsonic antibodies, B. parapertussis fails to activate resting neutrophils, thereby preventing bactericidal responses. We here investigated whether neutrophil priming with gamma-interferon (IFN-γ), the main proinflammatory cytokine present during infection, changes this outcome. We observed that IFN-γ- priming of neutrophils did not enhance extracellular nor intracellular bactericidal mechanisms against B. parapertussis. Human neutrophils remain basically unresponsive to this pathogen despite IFN-γ priming, and this lack of activation proved independent of adenylate cyclase toxin (CyaA), the immunomodulatory toxin produced by B. parapertussis. Collectively, our findings demonstrate that B. parapertussis does not trigger neutrophil activation, irrespective of the inflammatory context. This ability to evade a key arm of the innate immune response likely constitutes a critical pathogenic trait that, particularly in the absence of cross-protection conferred by current pertussis vaccines, underlies persistent infections and the continued circulation of the pathogen.