Canonical and non-canonical inflammasome activation by outer membrane vesicles derived from Bordetella pertussis

ELIZAGARAY MAIA; GOMES MARCO TULIO; GUIMARAES ERIKA; RUMBO MARTÍN; HOZBOR DANIELA; OLIVEIRA SERGIO C; MORENO GRISELDA

Frontiers in Immunology

Frontiers Media S.A.

Lugar: Laussane; Año: 2020

1664-3224

Outer Membrane Vesicles (OMVs) derived from differentGram negative bacteria have been proposed as an attractive vaccine platformbecause of their own immunogenic adjuvant properties. Pertussis or whooping coughis a highly contagious vaccine-preventable respiratory disease that resurgedduring the last decades in many countries. In response to this epidemiologicsituation new boosters have been incorporated into the vaccination schedulesand new vaccine candidates have started to be designed. In particular our groupdesigned a new pertussis vaccine candidate based on OMVs derived from Bordetellapertussis (BpOMVs). To continue with the characterization of the immuneresponse induced by our OMV based vaccine candidate in this work we investigatethe ability of OMVs to activate the inflammasome in macrophages. We detectedNLRP3, caspase-1/11 and gasdermin-D (GSDMD) are involved in inflammasomeactivation by BpOMVs. Moreover, we demonstrate that BpOMVs as well astransfected B. pertussis lipooligosaccharide (BpLOS) induce caspase-11(Casp11) and guanylate-binding proteins (GBPs) dependent non-canonicalinflammasome activation. Our results elucidate the mechanism of BpOMVs totrigger one central pathway of the innate response activation that is expectedto skew the adaptive immune response elicited by BpOMVs vaccination.