Outer Membrane Vesicles (OMVs) derived from different Gram-negative bacteria have been proposed as an attractive vaccine platform because of their own immunogenic adjuvant properties. Pertussis or whooping cough is a highly contagious vaccine-preventable respiratory disease that resurged during the last decades in many countries. In response to the epidemiological situation, new boosters have been incorporated into vaccination schedules worldwide and new vaccine candidates have started to be designed. Particularly, our group designed a new pertussis vaccine candidate based on OMVs derived from Bordetella pertussis (BpOMVs). To continue with the characterization of the immune response induced by our OMV based vaccine candidate, this work aimed to investigate the ability of OMVs to activate the inflammasome pathway in macrophages. We observed that NLRP3, caspase-1/11, and gasdermin-D (GSDMD) are involved in inflammasome activation by BpOMVs. Moreover, we demonstrated that BpOMVs as well as transfected B. pertussis lipooligosaccharide (BpLOS) induce caspase-11 (Casp11) and guanylate-binding proteins (GBPs) dependent non-canonical inflammasome activation. Our results elucidate the mechanism by which BpOMVs trigger one central pathway of the innate response activation that is expected to skew the adaptive immune response elicited by BpOMVs vaccination.

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Whooping cough, or pertussis, is a highly communicable infectious disease caused by the bacterium Bordetella pertussis. Vaccination once reduced the incidence of the disease, but a global resurgence of the infection happened during the past two decades, likely due to the waning immunity of vaccination. Macrolides such as erythromycin and azithromycin are the drugs of primary choice for treatment. In this personal view, we call for attention to macrolide-resistant B. pertussis (MRBP), which has emerged and prevailed in mainland China for years and are exclusively mediated by mutations in the 23S rRNA gene. Whether the prevalence of MRBP in China results from overuse of azithromycin in clinical medicine remains unknown. The incidence of MRBP is low in other countries, but this could be a technical illusion since China employs culture as the mainstream diagnostic method whereas nucleic-acid amplification test being widely used in other countries fail to test antimicrobial susceptibility. Given the increasingly frequent global travel that facilitates microbial transmission worldwide, there is a pressing need to perform international surveillance on MRBP to prevent the potential circulation of the organism. Finding alternative agents that possess good activity against B. pertussis is also urgently required.