title: Lipopeptides rather than lipopolysaccharide favor the development of dendritic cell dysfunction similar to polymicrobial sepsis in mice.
abstract: OBJECTIVE
  We investigated whether the dysfunction of dendritic cells (DC) that develops during polymicrobial sepsis is mimicked by systemic administration of the Toll-like receptor (TLR) 4 agonist lipopolysaccharide (LPS) or of the TLR2 agonist Pam3-Cys-Ser-Lys4 (P3CSK4).
  
  
  METHODS
  BALB/c mice underwent cecal ligation and puncture (CLP) or sham operation or received a single i.p. injection of LPS (30 mg/kg body weight), P3CSK4 (10 mg/kg body weight), or saline as control. Purified splenic DC and in-vitro-generated DC from bone marrow were analyzed in terms of surface marker expression, cytokine secretion, and antigen-specific T-cell activation in vivo.
  
  
  RESULTS
  Splenic DC were suppressed in IL-12 secretion 12 h after LPS and P3CSK4 administration but released increased levels of IL-12 4 days after TLR agonist application, unlike DC from CLP mice. Polymicrobial sepsis and TLR agonists caused a loss of DC in the spleen but led to the expansion of diverse DC subsets. DC that differentiated from bone marrow after P3CSK4 but not after LPS application resembled DC from CLP mice regarding cytokine secretion and impaired Th1-cell polarization.
  
  
  CONCLUSIONS
  The development of DC dysfunction during sepsis is at least partly mimicked by TLR2 agonists rather than TLR4 agonists.
authors.affiliation: Surgical Research, Department of Trauma Surgery, University Hospital Essen, University Duisburg-Essen, Virchowstr. 171, 45147 Essen, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Bruns
authors.forename: Eva
authors.initials: E
authors.lastname: Pastille
authors.forename: Florian
authors.initials: F
authors.lastname: Wirsdörfer
authors.forename: Marion
authors.initials: M
authors.lastname: Frisch
authors.forename: Stefanie B
authors.initials: SB
authors.lastname: Flohé
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D005260:Female; D055666:Lipopeptides / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008074:Lipoproteins / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018805:Sepsis / Q000276:immunology*; D013154:Spleen / Q000166:cytology; D051195:Toll-Like Receptor 2 / Q000819:agonists*; D051197:Toll-Like Receptor 4 / Q000819:agonists*
chemical_list: D055666:Lipopeptides; D008070:Lipopolysaccharides; D008074:Lipoproteins; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; C061108:N-palmitoyl-S-(2,3-bis(palmitoyloxy)propyl)cysteinyl-seryl-lysyl-lysyl-lysyl-lysine
references.citation: Infect Immun. 2009 Dec;77(12):5651-8
references.pmid: 19805530
references.citation: Nature. 1998 Mar 19;392(6673):245-52
references.pmid: 9521319
references.citation: J Immunol. 2004 Apr 15;172(8):4733-43
references.pmid: 15067049
references.citation: J Immunol. 2008 May 1;180(9):5771-7
references.pmid: 18424693
references.citation: J Immunol. 2011 Jan 15;186(2):977-86
references.pmid: 21160046
references.citation: J Immunol. 2005 Jul 15;175(2):839-46
references.pmid: 16002681
references.citation: J Immunol. 2003 Jul 15;171(2):909-14
references.pmid: 12847261
references.citation: Mol Med. 2008 May-Jun;14(5-6):247-56
references.pmid: 18297128
references.citation: Int Immunopharmacol. 2003 Aug;3(8):1217-24
references.pmid: 12860177
references.citation: Trends Immunol. 2009 Oct;30(10):475-87
references.pmid: 19781994
references.citation: J Infect Dis. 2012 Sep 15;206(6):932-42
references.pmid: 22782952
references.citation: J Immunol. 2007 Jan 15;178(2):1164-71
references.pmid: 17202381
references.citation: J Immunol. 2008 Dec 15;181(12):8513-20
references.pmid: 19050269
references.citation: Nat Immunol. 2000 Sep;1(3):199-205
references.pmid: 10973276
references.citation: J Immunol. 2002 Oct 1;169(7):3652-60
references.pmid: 12244157
references.citation: Eur J Immunol. 1998 Oct;28(10):3231-9
references.pmid: 9808192
references.citation: Crit Care Med. 2001 Jul;29(7):1303-10
references.pmid: 11445675
references.citation: J Immunol. 2004 Sep 1;173(5):3035-43
references.pmid: 15322163
references.citation: Semin Immunol. 2004 Feb;16(1):27-34
references.pmid: 14751761
references.citation: J Leukoc Biol. 2004 Mar;75(3):408-12
references.pmid: 14557384
references.citation: Blood. 2008 Feb 15;111(4):1797-804
references.pmid: 18055863
references.citation: J Exp Med. 1996 Oct 1;184(4):1413-24
references.pmid: 8879213
references.citation: J Immunol. 2000 Dec 15;165(12):6762-70
references.pmid: 11120796
references.citation: J Immunol Methods. 1999 Feb 1;223(1):77-92
references.pmid: 10037236
references.citation: J Immunol. 2001 Jun 15;166(12):7504-13
references.pmid: 11390504
references.citation: Nature. 1997 Mar 27;386(6623):336-7
references.pmid: 9121548
references.citation: J Immunol. 2001 May 1;166(9):5688-94
references.pmid: 11313410
references.citation: Shock. 2006 Dec;26(6):565-70
references.pmid: 17117130
references.citation: J Immunol. 2007 May 15;178(10):6173-80
references.pmid: 17475844
references.citation: Immunity. 2006 Jun;24(6):801-812
references.pmid: 16782035
references.citation: Blood. 2006 May 1;107(9):3656-64
references.pmid: 16410444
references.citation: Mol Immunol. 2007 Apr;44(10):2558-65
references.pmid: 17267035
references.citation: Shock. 2004 May;21(5):415-25
references.pmid: 15087817
references.citation: Science. 1999 Jul 30;285(5428):736-9
references.pmid: 10426996
references.citation: J Leukoc Biol. 2006 Mar;79(3):473-81
references.pmid: 16365154