Canonical and Non-canonical Inflammasome Activation by Outer Membrane Vesicles Derived From Bordetella pertussis

Area of Science:

• Immunology
• Vaccinology
• Microbiology

Background:

• Outer Membrane Vesicles (OMVs) from Gram-negative bacteria are promising vaccine platforms due to inherent adjuvant properties.
• Pertussis (whooping cough) is a contagious, vaccine-preventable respiratory illness with recent global resurgence.
• New pertussis vaccine candidates are being developed, including those based on Bordetella pertussis OMVs (BpOMVs).

Purpose of the Study:

• To investigate the inflammasome activation capacity of BpOMVs in macrophages.
• To elucidate the specific inflammasome pathways triggered by BpOMVs.
• To understand how BpOMVs contribute to innate immune response activation for vaccine development.

Main Methods:

• Macrophage inflammasome activation assays using BpOMVs.
• Analysis of inflammasome components: NLRP3, caspase-1/11, and gasdermin-D (GSDMD).
• Investigation of non-canonical inflammasome activation by BpOMVs and Bordetella pertussis lipooligosaccharide (BpLOS), including caspase-11 (Casp11) and guanylate-binding proteins (GBPs).

Main Results:

• BpOMVs activate the inflammasome pathway in macrophages, involving NLRP3, caspase-1/11, and GSDMD.
• BpOMVs and BpLOS induce caspase-11-dependent non-canonical inflammasome activation.
• Guanylate-binding proteins (GBPs) are implicated in the BpOMV-mediated inflammasome activation.

Conclusions:

• BpOMVs activate key innate immune pathways, specifically the inflammasome.
• The identified inflammasome activation mechanism provides insight into BpOMV vaccine efficacy.
• Understanding this pathway is essential for optimizing BpOMV-based pertussis vaccines.