IFN-γ and R-848 dependent activation of human monocyte-derived dendritic cells by Neisseria meningitidis adhesin A

Cristina Mazzon, Barbara Baldani-Guerra, Paola Cecchini, Tihana Kasic, Antonella Viola, Marina De Bernard, Beatrice Aricò, Franca Gerosa, Emanuele Papini

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Abstract

A soluble recombinant form of Neisseria meningitidis adhesin A (NadAΔ351-405), proposed as a constituent of anti-meningococcal B vaccines, is here shown to specifically interact with and immune-modulate human monocyte-derived dendritic cells (mo-DCs). After priming with IFN-γ and stimulation with NadAΔ351-405, mo-DCs strongly up-regulated maturation markers CD83, CD86, CD80, and HLA-DR, secreted moderate quantities of TNF-α, IL-6, and IL-8, and produced a slight, although significant, amount of IL-12p70. Costimulation of mo-DCs with NadAΔ351-405 and the imidoazoquinoline drug R-848, believed to mimic bacterial RNA, increased CD86 in an additive way, but strongly synergized the secretion of IL-12p70, IL-1, IL-6, TNF-α, and MIP-1α, especially after IFN-γ priming. CD86/CD80 overexpression correlated with the occupation of high-(kd ∼ 80 nM) and low-(kd ∼ 4 μM) affinity binding sites for NadAΔ351-405. Alternatively, secretion of IL-12p70 and TNF-α, IL-6, and IL-8 corresponded to the occupation of high- or low-affinity receptors, respectively. Mo-DCs matured by IFN-γ and NadAΔ351-405 supported the proliferation of naive CD4+ T lymphocytes, inducing the differentiation of both IFN-γ and IL-4 producing phenotypes. Our data show that NadA not only is a good immunogen but is as well endowed with a proimmune, self-adjuvating, activity.

Original languageEnglish
Pages (from-to)3904-3916
Number of pages13
JournalJournal of Immunology
Volume179
Issue number6
Publication statusPublished - Sep 15 2007

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resiquimod
Neisseria meningitidis
Dendritic Cells
Monocytes
Interleukin-6
Interleukin-8
Occupations
Bacterial RNA
Meningococcal Vaccines
HLA-DR Antigens
Interleukin-1
Interleukin-4
Binding Sites
T-Lymphocytes
Phenotype
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Immunology

Cite this

Mazzon, C., Baldani-Guerra, B., Cecchini, P., Kasic, T., Viola, A., De Bernard, M., ... Papini, E. (2007). IFN-γ and R-848 dependent activation of human monocyte-derived dendritic cells by Neisseria meningitidis adhesin A. Journal of Immunology, 179(6), 3904-3916.

IFN-γ and R-848 dependent activation of human monocyte-derived dendritic cells by Neisseria meningitidis adhesin A. / Mazzon, Cristina; Baldani-Guerra, Barbara; Cecchini, Paola; Kasic, Tihana; Viola, Antonella; De Bernard, Marina; Aricò, Beatrice; Gerosa, Franca; Papini, Emanuele.

In: Journal of Immunology, Vol. 179, No. 6, 15.09.2007, p. 3904-3916.

Research output: Contribution to journalArticle

Mazzon, C, Baldani-Guerra, B, Cecchini, P, Kasic, T, Viola, A, De Bernard, M, Aricò, B, Gerosa, F & Papini, E 2007, 'IFN-γ and R-848 dependent activation of human monocyte-derived dendritic cells by Neisseria meningitidis adhesin A', Journal of Immunology, vol. 179, no. 6, pp. 3904-3916.
Mazzon C, Baldani-Guerra B, Cecchini P, Kasic T, Viola A, De Bernard M et al. IFN-γ and R-848 dependent activation of human monocyte-derived dendritic cells by Neisseria meningitidis adhesin A. Journal of Immunology. 2007 Sep 15;179(6):3904-3916.
Mazzon, Cristina ; Baldani-Guerra, Barbara ; Cecchini, Paola ; Kasic, Tihana ; Viola, Antonella ; De Bernard, Marina ; Aricò, Beatrice ; Gerosa, Franca ; Papini, Emanuele. / IFN-γ and R-848 dependent activation of human monocyte-derived dendritic cells by Neisseria meningitidis adhesin A. In: Journal of Immunology. 2007 ; Vol. 179, No. 6. pp. 3904-3916.
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