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

Research output: Contribution to journalArticlepeer-review

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

ASJC Scopus subject areas

  • Immunology

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