Altered host immune responses to membrane vesicles from Salmonella and Gram-negative pathogens

摘要: Membrane vesicles (MVs), discrete nano-structures produced from the outer membrane of Gram-negative bacteria such as Salmonella enterica Typhimurium (S. Typhimurium), strongly activate dendritic cells (DCs), contain major antigens (Ags) recognized by Salmonella-specific B-cells and CD4+ T-cells, provide protection against S. challenge in a mouse model. With this mind, we hypothesized that alterations to gene expression profile will be reflected immunologic response MVs. To test this, assessed ability MVs wild-type (WT) or strain with phenotype mimicking intracellular-phase (PhoP(c)) initiate strong inflammatory response. MVs, isolated PhoP(c)S. (WTMVs PhoPcMVs, respectively) had pro-inflammatory properties consistent parental bacterial strains: PhoPcMVs were less stimulatory for DC activation vitro impaired subsequent responses compared WTMVs. Interestingly, reduced did not completely rely on signals through TLR4, receptor LPS. Nonetheless, both WTMVs contained abundant immunogenic capable being memory-immune T-cells mice previously infected Typhimurium. Furthermore, analyzed suite pathogenic their purified DCs stimulate inflammation manner known strains, shown Finally, analysis potential vaccine utility revealed capacity encapsulate an exogenous model antigen antigen-specific CD8+ T-cell responses. Taken together, our results demonstrate dependence cell MV immunogenicity response, well platform.