Dendritic cell activation and cytokine production induced by group B Neisseria meningitidis: Interleukin-12 production depends on lipopolysaccharide expression in intact bacteria

Interactions between dendritic cells (DCs) and microbial pathogens are fund amental to the generation of innate and adaptive immune responses. Upon sti mulation with bacteria or bacterial components such as lipopolysaccharide ( LPS), immature DCs undergo a maturation process that involves expression of costimulatory molecules, HLA molecules, and cytokines and chemokines, thus providing critical signals for lymphocyte development and differentiation. In this study, we investigated the response of in vitro-generated human DC s to a serogroup B strain of Neisseria meningitidis compared to an isogenic mutant lpxA strain totally deficient in LPS and purified LPS from the same strain. We show that the parent strain, lpxA mutant, and meningococcal LPS all induce DC maturation as measured by increased surface expression of co stimulatory molecules and HLA class I and II molecules. Both the parent and lpxA strains induced production of tumor necrosis factor alpha (TNF-alpha) , interleukin-1 alpha (IL-1 alpha), and IL-6 in DCs, although the parent wa s the more potent stimulus. In contrast, high-level IL-12 production was on ly seen with the parent strain. Compared to intact bacteria, purified LPS w as a very poor inducer of IL-1 alpha, IL-6, and TNF-alpha production and in duced no detectable IL-12, Addition of exogenous LPS to the lpxA strain onl y partially restored cytokine production and did not restore IL-12 producti on. These data show that non-LPS components of N. meningitidis induce DC ma turation, but that LPS in the context of the intact bacterium is required f or high-level cytokine production, especially that of IL-12, These findings may be useful in assessing components of N. meningitidis as potential vacc ine candidates.