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The differential response of human dendritic cells to live and killed Neisseria meningitidis

Jones, Hannah E.; Uronen-Hansson, Heli LU ; Callard, Robin E.; Klein, Nigel and Dixon, Garth L. J. (2007) In Cellular Microbiology 9(12). p.2856-2869
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,... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cellular Microbiology
volume
9
issue
12
pages
2856 - 2869
publisher
Wiley-Blackwell
external identifiers
  • wos:000250761100010
  • scopus:35948950236
ISSN
1462-5814
DOI
10.1111/j.1462-5822.2007.01001.x
language
English
LU publication?
yes
id
9a8f5d7e-1196-4d99-a58d-8b550fbf92fa (old id 974387)
date added to LUP
2008-01-29 14:37:14
date last changed
2017-01-15 03:35:50
@article{9a8f5d7e-1196-4d99-a58d-8b550fbf92fa,
  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.},
  author       = {Jones, Hannah E. and Uronen-Hansson, Heli and Callard, Robin E. and Klein, Nigel and Dixon, Garth L. J.},
  issn         = {1462-5814},
  language     = {eng},
  number       = {12},
  pages        = {2856--2869},
  publisher    = {Wiley-Blackwell},
  series       = {Cellular Microbiology},
  title        = {The differential response of human dendritic cells to live and killed Neisseria meningitidis},
  url          = {http://dx.doi.org/10.1111/j.1462-5822.2007.01001.x},
  volume       = {9},
  year         = {2007},
}