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Infection and Immunity, July 2001, p. 4351-4357, Vol. 69, No. 7
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.7.4351-4357.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Dendritic Cell Activation and Cytokine Production Induced by Group B Neisseria meningitidis: Interleukin-12 Production Depends on Lipopolysaccharide Expression in Intact Bacteria

Garth L. J. Dixon,1,* Phillippa J. Newton,2,3 Benjamin M. Chain,3 David Katz,3 Svein Rune Andersen,4 Simon Wong,4 Peter van der Ley,5 Nigel Klein,1 and Robin E. Callard1

Immunobiology Unit, Institute of Child Health, London WC1N 1EH,1 Department of Sexually Transmitted Diseases2 and Department of Immunology,3 Windeyer Institute, University College London, London WC1E 6BT, and Edward Jenner Institute for Vaccine Research, Compton, Berkshire RG20 7NN,4 United Kingdom, and National Institute of Public Health and the Environment, RIVM, 3720 BA Bilthoven, The Netherlands5

Received 26 January 2001/Returned for modification 21 March 2001/Accepted 10 April 2001

Interactions between dendritic cells (DCs) and microbial pathogens are fundamental to the generation of innate and adaptive immune responses. Upon stimulation with bacteria or bacterial components such as lipopolysaccharide (LPS), immature DCs undergo a maturation process that involves expression of costimulatory molecules, HLA molecules, and cytokines and chemokines, thus providing critical signals for lymphocyte development and differentiation. In this study, we investigated the response of in vitro-generated human DCs to a serogroup B strain of Neisseria meningitidis compared to an isogenic mutant lpxA strain totally deficient in LPS and purified LPS from the same strain. We show that the parent strain, lpxA mutant, and meningococcal LPS all induce DC maturation as measured by increased surface expression of costimulatory molecules and HLA class I and II molecules. Both the parent and lpxA strains induced production of tumor necrosis factor alpha (TNF-alpha ), interleukin-1alpha (IL-1alpha ), and IL-6 in DCs, although the parent was the more potent stimulus. In contrast, high-level IL-12 production was only seen with the parent strain. Compared to intact bacteria, purified LPS was a very poor inducer of IL-1alpha , IL-6, and TNF-alpha production and induced no detectable IL-12. Addition of exogenous LPS to the lpxA strain only partially restored cytokine production and did not restore IL-12 production. These data show that non-LPS components of N. meningitidis induce DC maturation, but that LPS in the context of the intact bacterium is required for high-level cytokine production, especially that of IL-12. These findings may be useful in assessing components of N. meningitidis as potential vaccine candidates.

* Corresponding author. Mailing address: Immunobiology Unit, Institute of Child Health, 30 Guilford St., London WC1N 1EH, United Kingdom. Phone: 44 207 905 2307. Fax: 44 207 813 8494. E-mail: G.Dixon{at}ich.ucl.ac.uk.

Infection and Immunity, July 2001, p. 4351-4357, Vol. 69, No. 7
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.7.4351-4357.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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