Human dendritic cell activation by Neisseria meningitidis: phagocytosis depends on expression of lipooligosaccharide (LOS) by the bacteria and is required for optimal cytokine production
(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:
https://lup.lub.lu.se/record/1297835
- author
- 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
- publishing date
- 2004
- 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
- pmid:15186399
- 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
- 2016-04-01 11:37:41
- date last changed
- 2022-01-26 07:48:46
@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}}, doi = {{10.1111/j.1462-5822.2004.00387.x}}, volume = {{6}}, year = {{2004}}, }