title: The differential response of human dendritic cells to live and killed Neisseria meningitidis.
abstract: There is currently no effective vaccine for Neisseria meningitidis (Nm) serogroup B. Generation of optimal immune responses to meningococci could be achieved by targeting meningococcal antigens to human dendritic cells (DCs). Recent studies have shown that diverse DC responses and subsequent generation of protective immunity can be observed if the microbes are viable or killed. This is important because the host is likely to be exposed to both live and killed bacteria during natural infection. There are currently few data on comparative DC responses to live and killed meningococci. We show here that exposure of human DC to live meningococci does not result in a typical maturation response, as determined by the failure to upregulate CD40, CD86, HLA-DR and HLA-Class I. Despite this, live meningococci were potent inducers of IL-12 and IL-10, although the ratios of these cytokines differed from those to killed organisms. Our data also suggest that enhanced phagocytosis of killed organisms compared with live may be responsible for the differential cytokine responses, involving an autocrine IL-10-dependent mechanism. The consequences of these findings upon the effectiveness of antigen presentation and T-cell responses are currently under investigation.
authors.affiliation: Infectious Diseases and Microbiology Unit and Immunobiology Unit, Institute of Child Health, UCL, London, UK.
authors.forename: Hannah E
authors.initials: HE
authors.lastname: Jones
authors.forename: Heli
authors.initials: H
authors.lastname: Uronen-Hansson
authors.forename: Robin E
authors.initials: RE
authors.lastname: Callard
authors.forename: Nigel
authors.initials: N
authors.lastname: Klein
authors.forename: Garth L J
authors.initials: GL
authors.lastname: Dixon
mesh_terms: D051940:B7-2 Antigen / Q000096:biosynthesis; D019013:CD40 Antigens / Q000096:biosynthesis; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D006684:HLA-DR Antigens / Q000096:biosynthesis; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D050296:Microbial Viability / Q000276:immunology*; D009345:Neisseria meningitidis / Q000276:immunology*; D010587:Phagocytosis / Q000276:immunology; D015854:Up-Regulation
chemical_list: D051940:B7-2 Antigen; D019013:CD40 Antigens; D006684:HLA-DR Antigens; D015395:Histocompatibility Antigens Class I; D016753:Interleukin-10; D018664:Interleukin-12