Open AccessHuman dendritic cell activation by Neisseria meningitidis : phagocytosis depends on expression of lipooligosaccharide (LOS) by the bacteria and is required for optimal cytokine production
Author(s) -
UronenHansson Heli,
Steeghs Liana,
Allen Jennifer,
Dixon Garth L. J.,
Osman Mohamed,
Van Der Ley Peter,
Wong Simon Y. C.,
Callard Robin,
Klein Nigel
Publication year - 2004
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/j.1462-5822.2004.00387.x
Subject(s) - neisseria meningitidis , internalization , microbiology and biotechnology , biology , bacteria , phagocytosis , immune system , cytokine , immunology , cell , genetics
Summary Group B Neisseria meningitidis is a human pathogen, for which a universally effective vaccine is still not available. Immune responses to bacteria are initiated by dendritic cells (DC), which internalize and process bacterial antigens for presentation to T cells. We show here that optimal IL‐12 and TNF‐α production by human monocyte derived DC in response to killed serogroup B N. meningitidis depends on physical contact and internalization of the bacteria by DC. The majority of DC producing cytokines had internalized N. meningitidis while inhibition of bacterial internalization markedly impaired IL‐12 and TNF‐α, but not IL‐6 production. Internalization of N. meningitidis was shown to depend on lipooligosaccharide (LOS) expressed by the bacteria with poor internalization of LOS deficient bacteria compared to wild‐type bacteria. Restoration of LOS biosynthesis in a LOS regulatory strain also restored both internalization and cytokine production and was enhanced in the presence of LPS binding protein (LBP). These results suggest that DC phagocytosis depends on expression of LOS within the bacteria and that optimal cytokine production, particularly IL‐12, requires internalization of the bacteria. These findings have important implications for designing vaccines that will induce protective immune responses to group B N. meningitidis.