title: The dendritic cell mannose receptor mediates allergen internalization and maturation involving notch 1 signalling.
abstract: Dendritic cells (DCs) have been shown recently to play a key role in inducing and mediating T helper type 2 (Th2) responses associated with atopic disease. These responses are mediated in part by ligation to different Toll-like receptors (TLRs) and C-type lectins, e.g. the mannose receptor (MR), depending upon the DC subset involved and the respective microenvironments. Because ovalbumin (OVA) (which is structurally related to various allergens) can engage the MR, we can use OVA stimulation as a model for understanding the roles of both TLRs and the MR in allergic inflammatory responses. We examined TLR- and MR-mediated responses from mouse bone marrow-derived DCs in the context of antigen recognition and presentation in addition to examining the relationship between notch 1, TLRs and MR signalling pathways. This work demonstrated that OVA-mediated signalling up-regulated both TLR-2 and MR and that MR RNA interference (RNAi) but not TLR2 RNAi inhibited DC internalization of fluorescein isothiocyanate-OVA. Furthermore, MR RNAi inhibited OVA- and house dust mite allergen extract-induced DC maturation and MR RNAi and TLR2 RNAi influenced DC interleukin-12 production independently. Finally, we demonstrated that blocking notch 1 signalling inhibited both notch 1 and TLR-2 expression but not MR expression levels. However, MR RNAi inhibited the expression of MR, TLR-2 and notch 1. These results indicate that MR is the primary receptor mediating the internalization of environmental allergen glycoproteins. In addition, TLR-2 and notch 1 play important roles in DC maturation and antigen presentation and signals originating from the MR and TLR-2 receptors converge with the notch 1 signalling pathway.
authors.affiliation: Department of Otolaryngology, The First Affiliated Hospital of Sun-Yat Sen University, Guangzhou, Guangdong, China.
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.forename: H
authors.initials: H
authors.lastname: Jiang
authors.forename: W
authors.initials: W
authors.lastname: Wen
authors.forename: J
authors.initials: J
authors.lastname: Zheng
authors.forename: G
authors.initials: G
authors.lastname: Xu
mesh_terms: D000485:Allergens / Q000276:immunology*; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology; D051940:B7-2 Antigen / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D004705:Endocytosis / Q000235:genetics / Q000276:immunology*; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D018664:Interleukin-12 / Q000378:metabolism; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism*; D008297:Male; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology / Q000378:metabolism; D034622:RNA Interference; D051881:Receptor, Notch1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism; D051193:Toll-Like Receptors / Q000235:genetics
chemical_list: D000485:Allergens; D039741:Antigens, Dermatophagoides; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D018664:Interleukin-12; D010047:Ovalbumin
references.citation: Immunity. 2007 May;26(5):605-16
references.pmid: 17462920
references.citation: J Immunol. 2001 Jan 1;166(1):249-55
references.pmid: 11123299
references.citation: Biochim Biophys Acta. 2002 Sep 19;1572(2-3):364-86
references.pmid: 12223280
references.citation: J Allergy Clin Immunol. 2004 Mar;113(3):482-8
references.pmid: 15007351
references.citation: Immunobiology. 2007;212(6):491-8
references.pmid: 17544833
references.citation: J Immunol. 2000 May 1;164(9):4507-12
references.pmid: 10779751
references.citation: J Immunol Methods. 1990 Sep 14;132(2):191-5
references.pmid: 2170533
references.citation: Immunol Rev. 2009 Jul;230(1):201-15
references.pmid: 19594638
references.citation: Br J Dermatol. 2008 Apr;158(4):691-7
references.pmid: 18241264
references.citation: Cancer Immunol Immunother. 2007 Aug;56(8):1133-41
references.pmid: 17139492
references.citation: J Biol Chem. 2001 Oct 5;276(40):37692-9
references.pmid: 11477091
references.citation: J Immunol. 2006 Jun 1;176(11):6770-6
references.pmid: 16709836
references.citation: Immunol Rev. 1997 Apr;156:199-209
references.pmid: 9176709
references.citation: J Immunol. 2002 Aug 1;169(3):1524-34
references.pmid: 12133980
references.citation: J Immunol. 2001 Oct 15;167(8):4458-67
references.pmid: 11591772
references.citation: Blood. 1992 Nov 1;80(9):2363-73
references.pmid: 1421407
references.citation: J Exp Med. 1995 May 1;181(5):1755-62
references.pmid: 7722452
references.citation: Immunol Rev. 1998 Jun;163:19-34
references.pmid: 9700499
references.citation: Blood. 2001 Aug 15;98(4):1135-41
references.pmid: 11493462
references.citation: Lancet. 2001 Oct 6;358(9288):1129-33
references.pmid: 11597666
references.citation: Respir Res. 2005 Sep 07;6:100
references.pmid: 16146574
references.citation: Int Immunol. 1998 Nov;10(11):1593-8
references.pmid: 9846688
references.citation: Biochem J. 1998 Aug 1;333 ( Pt 3):601-8
references.pmid: 9677318
references.citation: Nat Immunol. 2004 Oct;5(10):987-95
references.pmid: 15454922
references.citation: Annu Rev Immunol. 2004;22:33-54
references.pmid: 15032573
references.citation: Nat Rev Immunol. 2002 Mar;2(3):151-61
references.pmid: 11913066
references.citation: J Exp Med. 1999 Feb 1;189(3):587-92
references.pmid: 9927520
references.citation: Blood. 2007 Jan 15;109(2):507-15
references.pmid: 16973960
references.citation: J Clin Invest. 2000 Aug;106(4):551-9
references.pmid: 10953030
references.citation: J Exp Med. 2007 Jul 9;204(7):1653-64
references.pmid: 17591855
references.citation: J Allergy Clin Immunol. 2002 Nov;110(5):763-70
references.pmid: 12417886
references.citation: Nat Immunol. 2002 Feb;3(2):196-200
references.pmid: 11812998
references.citation: Biochem J. 1965 Feb;94:502-8
references.pmid: 14346091
references.citation: Int Immunol. 2005 Jan;17(1):1-14
references.pmid: 15585605
references.citation: Nat Rev Immunol. 2002 Feb;2(2):77-84
references.pmid: 11910898
references.citation: Int Arch Allergy Appl Immunol. 1977;55(1-6):47-53
references.pmid: 201571
references.citation: Nat Med. 2002 Sep;8(9):1024-32
references.pmid: 12145647
references.citation: Curr Opin Immunol. 2005 Feb;17(1):18-24
references.pmid: 15653305
references.citation: Cell. 2004 May 14;117(4):515-26
references.pmid: 15137944
references.citation: Ann Allergy. 1986 Feb;56(2):150-5
references.pmid: 3484919