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

Published online before print October 5, 2006

This Article Full Text (Reprint (PDF)) All Versions of this Article: jlb.0705385v1 81/1/221    most recent Alert me when this article is cited Alert me if a correction is posted 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 Assier, E. Articles by Mooney, N. Search for Related Content PubMed PubMed Citation Articles by Assier, E. Articles by Mooney, N.

© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0705385

Received for publication July 11, 2005.

Accepted for publication August 8, 2006.

Article

TLR7/8 agonists impair monocyte-derived dendritic cell differentiation and maturation

Eric Assier ^*, Alain Haziot ^*, Viviana Marin-Esteban ^*, Enrico Maggi , Dominique Charron* , and Nuala Mooney ^*@

*INSERM U662, Paris, France; Université Paris 7, Institut Universitaire d’Hématologie, Centre Hayem, Hôpital Saint-Louis, Paris, France; and Department of Internal Medicine, Immunoallergology and Respiratory Disease Unit, University of Florence, Florence, Italy

^@ To whom correspondence should be addressed. E-mail: nuala.mooney{at}paris7.jussieu.fr.

	Abstract

Pathogen recognition by TLR activates the innate immune response and is typically followed by the development of an adaptive immune response initiated by antigen presentation. Dendritic cells (DC) are the most efficient APC and express diverse TLRs, including TLR7 and -8, which have been identified recently as targets for ssRNA recognition during viral infection. We have studied the effect of TLR7/8 agonists on DC differentiation and maturation from human monocytes. The synthetic agonist Resiquimod (R-848) or the physiological agonist ssRNA impaired monocyte differentiation to DC phenotypically and functionally. Induced expression of the nonclassical MHC molecules of the CD1 family in DC was inhibited at the protein and mRNA levels, and antigen acquisition was inhibited. Proinflammatory cytokine (including IL-6, IL-8, TNF-, IL-1) and IL-10 production were induced during DC differentiation. Cross-talk between TLR4 and TLR7/8 was revealed as immature DC, which had been differentiated in the presence of R-848, and were insensitive to LPS-mediated maturation and cytokine production but still induced allostimulation. These data lead us to suggest that ongoing viral activation of TLR7/8 could alter the adaptive immune response by modifying DC differentiation and by down-regulating DC responsiveness to a subsequent bacterial TLR4-mediated signal.

Key Words: human • viral • antigen presentation

This article has been cited by other articles:

				V. Marin-Esteban, M. Abdul, D. Charron, A. Haziot, and N. Mooney Dendritic Cells Differentiated in the Presence of a Single-Stranded Viral RNA Sequence Conserve Their Ability To Activate CD4 T Lymphocytes but Lose Their Capacity for Th1 Polarization Clin. Vaccine Immunol., June 1, 2008; 15(6): 954 - 962. [Abstract] [Full Text] [PDF]

				A. Seubert, E. Monaci, M. Pizza, D. T. O'Hagan, and A. Wack The Adjuvants Aluminum Hydroxide and MF59 Induce Monocyte and Granulocyte Chemoattractants and Enhance Monocyte Differentiation toward Dendritic Cells J. Immunol., April 15, 2008; 180(8): 5402 - 5412. [Abstract] [Full Text] [PDF]