Human dendritic cell activation by Neisseria meningitidis: Phagocytosis depends on expression of lipooligosaccharide (LOS) by the bacteria and is required for optimal cytokine production

H. Uronen-Hansson, L. Steeghs, J. Allen, G. L. J. Dixon, M. Osman, P. Van Der Ley, Simon Yuk Chun Wong, R. Callard, N. Klein

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

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-alpha 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-alpha, 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.

Original languageEnglish
Pages (from-to)625-637
Number of pages12
JournalCellular Microbiology
Volume6
DOIs
Publication statusPublished - 2004

Keywords

  • GRAM-NEGATIVE BACTERIA
  • TOLL-LIKE RECEPTORS
  • INTERLEUKIN-12 PRODUCTION
  • ANTIGEN PRESENTATION
  • GOLGI-APPARATUS
  • LIPOPOLYSACCHARIDE
  • RECOGNITION
  • MACROPHAGES
  • INDUCTION
  • ENDOTOXIN

Cite this

Human dendritic cell activation by Neisseria meningitidis: Phagocytosis depends on expression of lipooligosaccharide (LOS) by the bacteria and is required for optimal cytokine production. / Uronen-Hansson, H.; Steeghs, L.; Allen, J.; Dixon, G. L. J.; Osman, M.; Van Der Ley, P.; Wong, Simon Yuk Chun; Callard, R.; Klein, N.

In: Cellular Microbiology, Vol. 6, 2004, p. 625-637.

Research output: Contribution to journalArticle

Uronen-Hansson, H. ; Steeghs, L. ; Allen, J. ; Dixon, G. L. J. ; Osman, M. ; Van Der Ley, P. ; Wong, Simon Yuk Chun ; Callard, R. ; Klein, N. / Human dendritic cell activation by Neisseria meningitidis: Phagocytosis depends on expression of lipooligosaccharide (LOS) by the bacteria and is required for optimal cytokine production. In: Cellular Microbiology. 2004 ; Vol. 6. pp. 625-637.
@article{95d8d3dc32bc45e7bf0dc8f3ae28a9c0,
title = "Human dendritic cell activation by Neisseria meningitidis: Phagocytosis depends on expression of lipooligosaccharide (LOS) by the bacteria and is required for optimal cytokine production",
abstract = "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-alpha 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-alpha, 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.",
keywords = "GRAM-NEGATIVE BACTERIA, TOLL-LIKE RECEPTORS, INTERLEUKIN-12 PRODUCTION, ANTIGEN PRESENTATION, GOLGI-APPARATUS, LIPOPOLYSACCHARIDE, RECOGNITION, MACROPHAGES, INDUCTION, ENDOTOXIN",
author = "H. Uronen-Hansson and L. Steeghs and J. Allen and Dixon, {G. L. J.} and M. Osman and {Van Der Ley}, P. and Wong, {Simon Yuk Chun} and R. Callard and N. Klein",
year = "2004",
doi = "10.1111/j.1462-5822.2004.00387.x",
language = "English",
volume = "6",
pages = "625--637",
journal = "Cellular Microbiology",
issn = "1462-5814",
publisher = "Wiley-Blackwell",

}

TY - JOUR

T1 - Human dendritic cell activation by Neisseria meningitidis: Phagocytosis depends on expression of lipooligosaccharide (LOS) by the bacteria and is required for optimal cytokine production

AU - Uronen-Hansson, H.

AU - Steeghs, L.

AU - Allen, J.

AU - Dixon, G. L. J.

AU - Osman, M.

AU - Van Der Ley, P.

AU - Wong, Simon Yuk Chun

AU - Callard, R.

AU - Klein, N.

PY - 2004

Y1 - 2004

N2 - 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-alpha 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-alpha, 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.

AB - 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-alpha 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-alpha, 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.

KW - GRAM-NEGATIVE BACTERIA

KW - TOLL-LIKE RECEPTORS

KW - INTERLEUKIN-12 PRODUCTION

KW - ANTIGEN PRESENTATION

KW - GOLGI-APPARATUS

KW - LIPOPOLYSACCHARIDE

KW - RECOGNITION

KW - MACROPHAGES

KW - INDUCTION

KW - ENDOTOXIN

U2 - 10.1111/j.1462-5822.2004.00387.x

DO - 10.1111/j.1462-5822.2004.00387.x

M3 - Article

VL - 6

SP - 625

EP - 637

JO - Cellular Microbiology

JF - Cellular Microbiology

SN - 1462-5814

ER -