Effects of surface-exposed sialic acid and LOS outer core on the ability of native Neisseria meningitidis outer membrane vesicles (nOMVs) to induce cytokine expression and pyroptotic pathways in THP-1-derived macrophages

Native outer membrane vesicles (nOMVs) are involved in meningococcal pathogenesis and are used for vaccine production. In this study, macrophages derived from the human monocytic cell line THP-1 were exposed to nOMVs from serogroup B N. meningitidis B1940 and derivative mutants B1940 siaD(+C), lacking the capsule, and B1940 cps, lacking both the capsule and the LOS outer core with sialic acid. Compared with THP-1 cells exposed to B1940 nOMVs, cells exposed to B1940 cps nOMVs showed significantly lower mRNA levels of genes encoding chemokines, interleukins, caspases, and gasdermin E (DFNA5). Furthermore, Western blot analysis showed a reduction in pro-IL-1β expression and activation of gasdermin E and caspase-4 in THP-1 macrophages treated with B1940 cps nOMVs compared to B1940 or B1940 siaD(+C) nOMVs. However, secreted pro-IL-1β and IL-1β were detected in the culture medium of THP-1 cells exposed to B1940 siaD(+C) nOMVs but not to B1940 or B1940 cps nOMVs. These findings provide genetic evidence that surface-exposed sialic acid and LOS outer core may contribute to the ability of meningococcal nOMVs to activate cytokine expression and pyroptotic pathways in THP-1-derived macrophages, providing new information to create safe nOMV-based vaccines.