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
摘要
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.