Dendritic cell activation and cytokine production induced by Group B Neisseria meningitidis: IL-12 production requires lipopolysaccharide to be expressed in intact bacteria

G. L. J. Dixon, P. Newton, B. Chain, S. R. Andersen, Simon Yuk Chun Wong, P. Van Der Ley, N. Klein, R. Callard

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

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-1 alpha (IL-1 alpha), 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-1 alpha, 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.

Original languageEnglish
Pages (from-to)4351-4357
Number of pages6
JournalInfection and Immunity
Volume69
DOIs
Publication statusPublished - 2001

Keywords

  • TOLL-LIKE RECEPTORS
  • INFLAMMATORY CYTOKINES
  • IL-12 PRODUCTION
  • IMMUNE-RESPONSE
  • TH1 CELLS
  • ENDOTOXIN
  • MATURATION
  • IMMUNIZATION
  • MECHANISMS
  • CHEMOKINES

Cite this

Dendritic cell activation and cytokine production induced by Group B Neisseria meningitidis: IL-12 production requires lipopolysaccharide to be expressed in intact bacteria. / Dixon, G. L. J.; Newton, P.; Chain, B.; Andersen, S. R.; Wong, Simon Yuk Chun; Van Der Ley, P.; Klein, N.; Callard, R.

In: Infection and Immunity, Vol. 69, 2001, p. 4351-4357.

Research output: Contribution to journalArticle

Dixon, G. L. J. ; Newton, P. ; Chain, B. ; Andersen, S. R. ; Wong, Simon Yuk Chun ; Van Der Ley, P. ; Klein, N. ; Callard, R. / Dendritic cell activation and cytokine production induced by Group B Neisseria meningitidis: IL-12 production requires lipopolysaccharide to be expressed in intact bacteria. In: Infection and Immunity. 2001 ; Vol. 69. pp. 4351-4357.
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T1 - Dendritic cell activation and cytokine production induced by Group B Neisseria meningitidis: IL-12 production requires lipopolysaccharide to be expressed in intact bacteria

AU - Dixon, G. L. J.

AU - Newton, P.

AU - Chain, B.

AU - Andersen, S. R.

AU - Wong, Simon Yuk Chun

AU - Van Der Ley, P.

AU - Klein, N.

AU - Callard, R.

PY - 2001

Y1 - 2001

N2 - 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-1 alpha (IL-1 alpha), 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-1 alpha, 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.

AB - 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-1 alpha (IL-1 alpha), 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-1 alpha, 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.

KW - TOLL-LIKE RECEPTORS

KW - INFLAMMATORY CYTOKINES

KW - IL-12 PRODUCTION

KW - IMMUNE-RESPONSE

KW - TH1 CELLS

KW - ENDOTOXIN

KW - MATURATION

KW - IMMUNIZATION

KW - MECHANISMS

KW - CHEMOKINES

U2 - 10.1128/IAI.69.7.4351-4357.2001

DO - 10.1128/IAI.69.7.4351-4357.2001

M3 - Article

VL - 69

SP - 4351

EP - 4357

JO - Infection and Immunity

JF - Infection and Immunity

SN - 0019-9567

ER -