DC-SIGN ligation on dendritic cells results in ERK and PI3K activation and modulates cytokine production - PubMed (original) (raw)
. 2006 May 15;107(10):3950-8.
doi: 10.1182/blood-2005-03-1252. Epub 2006 Jan 24.
Affiliations
- PMID: 16434485
- DOI: 10.1182/blood-2005-03-1252
Free article
DC-SIGN ligation on dendritic cells results in ERK and PI3K activation and modulates cytokine production
Esther Caparrós et al. Blood. 2006.
Free article
Abstract
The generation of pathogen-specific immune responses is dependent on the signaling capabilities of pathogen-recognition receptors. DC-SIGN is a C-type lectin that mediates capture and internalization of viral, bacterial, and fungal pathogens by myeloid dendritic cells. DC-SIGN-interacting pathogens are thought to modulate dendritic cell maturation by interfering with intracellular signaling from Toll-like receptor molecules. We report that engagement of DC-SIGN by specific antibodies does not promote dendritic cell maturation but induces ERK1/2 and Akt phosphorylation without concomitant p38MAPK activation. DC-SIGN ligation also triggers PLCgamma phosphorylation and transient increases in intracellular calcium in dendritic cells. In agreement with its signaling capabilities, a fraction of DC-SIGN molecules partitions within lipid raft-enriched membrane fractions both in DC-SIGN-transfected and dendritic cells. Moreover, DC-SIGN in dendritic cells coprecipitates with the tyrosine kinases Lyn and Syk. The relevance of the DC-SIGN-initiated signals was demonstrated in monocyte-derived dendritic cells, as DC-SIGN cross-linking synergizes with TNF-alpha for IL-10 release and enhances the production of LPS-induced IL-10. These results demonstrate that DC-SIGN-triggered intracellular signals modulate dendritic cell maturation. Since pathogens stimulate Th2 responses via preferential activation of ERK1/2, these results provide a molecular explanation for the ability of DC-SIGN-interacting pathogens to preferentially evoke Th2-type immune responses.
Similar articles
- Dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin mediates binding and internalization of Aspergillus fumigatus conidia by dendritic cells and macrophages.
Serrano-Gómez D, Domínguez-Soto A, Ancochea J, Jimenez-Heffernan JA, Leal JA, Corbí AL. Serrano-Gómez D, et al. J Immunol. 2004 Nov 1;173(9):5635-43. doi: 10.4049/jimmunol.173.9.5635. J Immunol. 2004. PMID: 15494514 - DC-SIGN ligation greatly affects dendritic cell differentiation from monocytes compromising their normal function.
Svajger U, Obermajer N, Anderluh M, Kos J, Jeras M. Svajger U, et al. J Leukoc Biol. 2011 Jun;89(6):893-905. doi: 10.1189/jlb.0810463. Epub 2011 Mar 29. J Leukoc Biol. 2011. PMID: 21447648 - Carbohydrate signaling by C-type lectin DC-SIGN affects NF-kappaB activity.
Gringhuis SI, Geijtenbeek TB. Gringhuis SI, et al. Methods Enzymol. 2010;480:151-64. doi: 10.1016/S0076-6879(10)80008-4. Methods Enzymol. 2010. PMID: 20816209 Review. - DC-SIGN mediated sphingomyelinase-activation and ceramide generation is essential for enhancement of viral uptake in dendritic cells.
Avota E, Gulbins E, Schneider-Schaulies S. Avota E, et al. PLoS Pathog. 2011 Feb;7(2):e1001290. doi: 10.1371/journal.ppat.1001290. Epub 2011 Feb 17. PLoS Pathog. 2011. PMID: 21379338 Free PMC article. - Glycan-based DC-SIGN targeting vaccines to enhance antigen cross-presentation.
van Kooyk Y, Unger WW, Fehres CM, Kalay H, García-Vallejo JJ. van Kooyk Y, et al. Mol Immunol. 2013 Sep;55(2):143-5. doi: 10.1016/j.molimm.2012.10.031. Epub 2012 Nov 14. Mol Immunol. 2013. PMID: 23158834 Review.
Cited by
- Metformin Uniquely Prevents Thrombosis by Inhibiting Platelet Activation and mtDNA Release.
Xin G, Wei Z, Ji C, Zheng H, Gu J, Ma L, Huang W, Morris-Natschke SL, Yeh JL, Zhang R, Qin C, Wen L, Xing Z, Cao Y, Xia Q, Lu Y, Li K, Niu H, Lee KH, Huang W. Xin G, et al. Sci Rep. 2016 Nov 2;6:36222. doi: 10.1038/srep36222. Sci Rep. 2016. PMID: 27805009 Free PMC article. - The effect of human immunodeficiency virus-1 on monocyte-derived dendritic cell maturation and function.
Fairman P, Angel JB. Fairman P, et al. Clin Exp Immunol. 2012 Oct;170(1):101-13. doi: 10.1111/j.1365-2249.2012.04628.x. Clin Exp Immunol. 2012. PMID: 22943206 Free PMC article. - HIV-1 gp120 mannoses induce immunosuppressive responses from dendritic cells.
Shan M, Klasse PJ, Banerjee K, Dey AK, Iyer SP, Dionisio R, Charles D, Campbell-Gardener L, Olson WC, Sanders RW, Moore JP. Shan M, et al. PLoS Pathog. 2007 Nov;3(11):e169. doi: 10.1371/journal.ppat.0030169. PLoS Pathog. 2007. PMID: 17983270 Free PMC article. - An anti-inflammatory property of Candida albicans β-glucan: Induction of high levels of interleukin-1 receptor antagonist via a Dectin-1/CR3 independent mechanism.
Smeekens SP, Gresnigt MS, Becker KL, Cheng SC, Netea SA, Jacobs L, Jansen T, van de Veerdonk FL, Williams DL, Joosten LA, Dinarello CA, Netea MG. Smeekens SP, et al. Cytokine. 2015 Feb;71(2):215-22. doi: 10.1016/j.cyto.2014.10.013. Epub 2014 Nov 20. Cytokine. 2015. PMID: 25461401 Free PMC article. - Extensive Phenotype of Human Inflammatory Monocyte-Derived Dendritic Cells.
Coutant F, Pin JJ, Miossec P. Coutant F, et al. Cells. 2021 Jul 2;10(7):1663. doi: 10.3390/cells10071663. Cells. 2021. PMID: 34359833 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous