Advanced

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, Heli LU ; Steeghs, Liana; Allen, Jennifer; Dixon, Garth L J; Osman, Mohamed; van der Ley, Peter; Wong, Simon Y C; Callard, Robin and Klein, Nigel (2004) In Cellular Microbiology 6(7). p.625-637
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
publishing date
type
Contribution to journal
publication status
published
subject
in
Cellular Microbiology
volume
6
issue
7
pages
625 - 637
publisher
Wiley-Blackwell
external identifiers
  • wos:000221853100003
  • scopus:2342422068
ISSN
1462-5814
DOI
10.1111/j.1462-5822.2004.00387.x
language
English
LU publication?
no
id
549789c9-1d57-4710-a0cb-3673dc39d04b (old id 1297835)
date added to LUP
2009-07-13 15:47:31
date last changed
2017-01-01 04:23:08
@article{549789c9-1d57-4710-a0cb-3673dc39d04b,
  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.},
  author       = {Uronen-Hansson, Heli and Steeghs, Liana and Allen, Jennifer and Dixon, Garth L J and Osman, Mohamed and van der Ley, Peter and Wong, Simon Y C and Callard, Robin and Klein, Nigel},
  issn         = {1462-5814},
  language     = {eng},
  number       = {7},
  pages        = {625--637},
  publisher    = {Wiley-Blackwell},
  series       = {Cellular Microbiology},
  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},
  url          = {http://dx.doi.org/10.1111/j.1462-5822.2004.00387.x},
  volume       = {6},
  year         = {2004},
}