title: BDCA1-positive dendritic cells (DCs) represent a unique human myeloid DC subset that induces innate and adaptive immune responses to Staphylococcus aureus Infection.
abstract: Staphylococcus aureus bloodstream infection (bacteremia) is a major cause of morbidity and mortality and places substantial cost burdens on health care systems. The role of peripheral blood dendritic cells (PBDCs) in the immune responses against S. aureus infection has not been well characterized. In this study, we demonstrated that BDCA1(+) myeloid DCs (mDCs) represent a unique PBDC subset that can induce immune responses against S. aureus infection. BDCA1(+) mDCs could engulf S. aureus and strongly upregulated the expression of costimulatory molecules and production of proinflammatory cytokines. Furthermore, BDCA1(+) mDCs expressed high levels of major histocompatibility complex (MHC) class I and II molecules in response to S. aureus and greatly promoted proliferation and gamma interferon (IFN-γ) production in CD4 and CD8 T cells. Moreover, BDCA1(+) mDCs expressed higher levels of Toll-like receptor 2 (TLR-2) and scavenger receptor A (SR-A) than those on CD16(+) and BDCA3(+) mDCs, and these two receptors were both required for the recognition of S. aureus and the subsequent activation of BDCA1(+) mDCs. Finally, BDCA1(+) mDC-mediated immune responses against S. aureus were dependent on MyD88 signaling pathways. These results demonstrate that human BDCA1(+) mDCs represent a unique subset of mDCs that can respond to S. aureus to undergo maturation and activation and to induce Th1 and Tc1 immune responses.
authors.affiliation: Shanghai Public Health Clinical Center, Shanghai Medical College, Fudan University, Shanghai, China. Junojin1@gmail.com.
authors.forename: Jun-O
authors.identifier: http://orcid.org/0000-0003-4216-8111
authors.initials: JO
authors.lastname: Jin
authors.affiliation: Shanghai Public Health Clinical Center, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Shanghai Public Health Clinical Center, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Jiang-Yuan
authors.initials: JY
authors.lastname: Du
authors.affiliation: Shanghai Public Health Clinical Center, Shanghai Medical College, Fudan University, Shanghai, China Department of Immunology and Infectious Diseases, The Forsyth Institute, Cambridge, Massachusetts, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Yu
mesh_terms: D056704:Adaptive Immunity / Q000502:physiology*; D000328:Adult; D000906:Antibodies; D018949:Antigens, CD1 / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology*; D008297:Male; D051117:Scavenger Receptors, Class A / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D013211:Staphylococcus aureus / Q000502:physiology*; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D000906:Antibodies; D018949:Antigens, CD1; C437944:CD1C protein, human; D006023:Glycoproteins; D051117:Scavenger Receptors, Class A; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2
references.citation: Blood. 2002 Dec 15;100(13):4512-20
references.pmid: 12393628
references.citation: Nature. 1998 Mar 19;392(6673):245-52
references.pmid: 9521319
references.citation: BMC Infect Dis. 2011 Oct 31;11:298
references.pmid: 22040268
references.citation: Exp Cell Res. 2007 Apr 15;313(7):1438-48
references.pmid: 17362929
references.citation: Future Microbiol. 2011 Jan;6(1):43-56
references.pmid: 21162635
references.citation: J Exp Med. 2010 Jun 7;207(6):1247-60
references.pmid: 20479116
references.citation: PLoS One. 2013 Sep 13;8(9):e74287
references.pmid: 24058538
references.citation: Semin Immunol. 2004 Feb;16(1):3-9
references.pmid: 14751757
references.citation: J Infect Dis. 2011 Feb 15;203(4):473-8
references.pmid: 21233310
references.citation: J Immunol. 2012 Feb 1;188(3):1234-44
references.pmid: 22219328
references.citation: Curr Opin Immunol. 2008 Feb;20(1):89-95
references.pmid: 18249105
references.citation: Crit Care Med. 2003 Apr;31(4):1250-6
references.pmid: 12682500
references.citation: J Immunol. 2006 Dec 1;177(11):8154-63
references.pmid: 17114491
references.citation: Nat Rev Immunol. 2007 Jul;7(7):543-55
references.pmid: 17589544
references.citation: J Exp Med. 2010 Jun 7;207(6):1273-81
references.pmid: 20479115
references.citation: J Immunol. 2000 Nov 15;165(10):5392-6
references.pmid: 11067888
references.citation: J Exp Med. 2010 Jun 7;207(6):1261-71
references.pmid: 20479117
references.citation: Blood. 2013 Aug 8;122(6):932-42
references.pmid: 23794066
references.citation: Am J Pathol. 2012 Oct;181(4):1327-37
references.pmid: 22885107
references.citation: Mol Immunol. 2007 Mar;44(9):2315-23
references.pmid: 17173973
references.citation: J Immunol. 2012 Oct 15;189(8):4040-6
references.pmid: 22962685
references.citation: N Engl J Med. 1998 Aug 20;339(8):520-32
references.pmid: 9709046
references.citation: Nature. 2005 Feb 3;433(7025):523-7
references.pmid: 15690042
references.citation: Curr Opin Infect Dis. 2010 Aug;23(4):346-58
references.pmid: 20592532
references.citation: Nat Rev Immunol. 2005 Apr;5(4):296-306
references.pmid: 15803149
references.citation: Infect Immun. 2000 Apr;68(4):1953-63
references.pmid: 10722588
references.citation: J Leukoc Biol. 2009 Apr;85(4):595-605
references.pmid: 19112093
references.citation: J Exp Med. 2013 May 6;210(5):1035-47
references.pmid: 23569327
references.citation: Clin Microbiol Rev. 2005 Jul;18(3):521-40
references.pmid: 16020688
references.citation: Cell. 2002 Dec 27;111(7):927-30
references.pmid: 12507420
references.citation: Science. 2004 May 14;304(5673):1014-8
references.pmid: 15143282
references.citation: PLoS One. 2014 Jan 31;9(1):e87927
references.pmid: 24498223
references.citation: J Immunol. 2010 Jun 15;184(12):7071-81
references.pmid: 20483752
references.citation: Adv Cancer Res. 2008;99:363-407
references.pmid: 18037410
references.citation: Mar Drugs. 2012 Oct;10(10):2337-48
references.pmid: 23170088
references.citation: J Immunol. 2012 Sep 15;189(6):3178-87
references.pmid: 22891282
references.citation: Lancet Infect Dis. 2011 Mar;11(3):208-22
references.pmid: 21371655
references.citation: Nat Med. 2004 Aug;10(8):842-8
references.pmid: 15247912
references.citation: Am J Transplant. 2013 Mar;13 Suppl 4:50-8
references.pmid: 23464998
references.citation: Methods Mol Biol. 2010;595:45-54
references.pmid: 19941104
references.citation: J Immunol. 2000 Mar 15;164(6):2978-86
references.pmid: 10706685
references.citation: Blood. 2009 Jun 4;113(23):5839-47
references.pmid: 19351958
references.citation: J Exp Med. 2010 Jun 7;207(6):1131-4
references.pmid: 20513744
references.citation: J Biol Chem. 2012 Jun 22;287(26):21663-72
references.pmid: 22547074
references.citation: Clin Microbiol Infect. 2013 Jun;19(6):492-500
references.pmid: 23398633
references.citation: J Biol Chem. 2011 Feb 11;286(6):4854-70
references.pmid: 21123169
references.citation: Blood. 1997 Nov 1;90(9):3245-87
references.pmid: 9345009
references.citation: J Immunol. 2011 Jan 1;186(1):443-52
references.pmid: 21131426