HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mazzon, C. Articles by Papini, E. Search for Related Content PubMed PubMed Citation Articles by Mazzon, C. Articles by Papini, E.

IFN- and R-848 Dependent Activation of Human Monocyte-Derived Dendritic Cells by Neisseria meningitidis Adhesin A¹

Cristina Mazzon^*, Barbara Baldani-Guerra, Paola Cecchini^*, Tihana Kasic, Antonella Viola, Marina de Bernard, Beatrice Aricò^¶, Franca Gerosa^2, and Emanuele Papini^2,3,*

^* Centro Ricerche Interdipartimentale Biotecnologie Innovative and Dipartimento di Scienze Biomediche Sperimentali, Università di Padova, Padova, Italy; Dipartimento di Patologia, Sezione di Immunologia, Università di Verona, Verona, Italy; Istituto Veneto Medicina Molecolare and Dipartimento di Scienze Biomediche Sperimentali, Università di Padova, Padova, Italy; Istituto Veneto Medicina Molecolare and Dipartimento di Biologia, Università di Padova, Padova, Italy; and ^¶ Research Centre, Novartis Vaccines and Diagnostics, Siena, Italy

A soluble recombinant form of Neisseria meningitidis adhesin A (NadA351–405), 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- and stimulation with NadA351–405, mo-DCs strongly up-regulated maturation markers CD83, CD86, CD80, and HLA-DR, secreted moderate quantities of TNF-, IL-6, and IL-8, and produced a slight, although significant, amount of IL-12p70. Costimulation of mo-DCs with NadA351–405 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-, and MIP-1, especially after IFN- priming. CD86/CD80 overexpression correlated with the occupation of high-(k_d 80 nM) and low-(k_d 4 µM) affinity binding sites for NadA351–405. Alternatively, secretion of IL-12p70 and TNF-, IL-6, and IL-8 corresponded to the occupation of high- or low-affinity receptors, respectively. Mo-DCs matured by IFN- and NadA351–405 supported the proliferation of naive CD4⁺ T lymphocytes, inducing the differentiation of both IFN- 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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by PRIN 2002 and 2003 grants from Italian Ministero Universitá e Ricerca, from Progetto d’Ateneo of the University of Padova and from Fondazione CARIVERONA (bandi 2003, 2004, and 2006).

² F.G. and E.P. contributed equally to the work.

³ Address correspondence and reprint requests to Dr. Emanuele Papini, Padua University, Via G. Colombo 3, Padua, Italy. E-mail address: emanuele.papini{at}unipd.it

⁴ Abbreviations used in this paper: DCs, dendritic cell; CHO, Chinese hamster ovary; HMBS, hydroxymethylbilane synthase; PAMP, pathogen-associated molecular pattern; MFI, mean fluorescence intensity.

This article has been cited by other articles:

				S. Franzoso, C. Mazzon, M. Sztukowska, P. Cecchini, T. Kasic, B. Capecchi, R. Tavano, and E. Papini Human monocytes/macrophages are a target of Neisseria meningitidis Adhesin A (NadA) J. Leukoc. Biol., May 1, 2008; 83(5): 1100 - 1110. [Abstract] [Full Text] [PDF]