title: Campylobacter jejuni lipooligosaccharide sialylation, phosphorylation, and amide/ester linkage modifications fine-tune human Toll-like receptor 4 activation.
abstract: Campylobacter jejuni is a leading cause of acute gastroenteritis. C. jejuni lipooligosaccharide (LOS) is a potent activator of Toll-like receptor (TLR) 4-mediated innate immunity. Structural variations of the LOS have been previously reported in the oligosaccharide (OS) moiety, the disaccharide lipid A (LA) backbone, and the phosphorylation of the LA. Here, we studied LOS structural variation between C. jejuni strains associated with different ecological sources and analyzed their ability to activate TLR4 function. MALDI-TOF MS was performed to characterize structural variation in both the OS and LA among 15 different C. jejuni isolates. Cytokine induction in THP-1 cells and primary monocytes was correlated with LOS structural variation in each strain. Additionally, structural variation was correlated with the source of each strain. OS sialylation, increasing abundance of LA d-glucosamine versus 2,3-diamino-2,3-dideoxy-d-glucose, and phosphorylation status all correlated with TLR4 activation as measured in THP-1 cells and monocytes. Importantly, LOS-induced inflammatory responses were similar to those elicited by live bacteria, highlighting the prominent contribution of the LOS component in driving host immunity. OS sialylation status but not LA structure showed significant association with strains clustering with livestock sources. Our study highlights how variations in three structural components of C. jejuni LOS alter TLR4 activation and consequent monocyte activation.
authors: Infectious Diseases and Microbiology Unit, Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, United Kingdom.
authors: Holly N
authors: HN
authors: Stephenson
authors: Constance M
authors: CM
authors: John
authors: Neveda
authors: N
authors: Naz
authors: Ozan
authors: O
authors: Gundogdu
authors: Nick
authors: N
authors: Dorrell
authors: Brendan W
authors: BW
authors: Wren
authors: Gary A
authors: GA
authors: Jarvis
authors: Mona
authors: M
authors: Bajaj-Elliott
mesh_terms: D016123:Campylobacter jejuni / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002236:Carbohydrate Conformation; D045744:Cell Line, Tumor; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D010766:Phosphorylation; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: D008070:Lipopolysaccharides; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; C023023:lipid-linked oligosaccharides
keywords: Campylobacter; Innate Immunity; Lipopolysaccharide (LPS); Monocytes; Toll-like Receptors (TLR)
references: PLoS Pathog. 2011 Dec;7(12):e1002454
references: 22216004
references: J Immunol. 2010 Dec 1;185(11):6974-84
references: 21037101
references: Infect Immun. 1987 Jan;55(1):174-80
references: 3098684
references: J Bacteriol. 2008 Aug;190(16):5681-9
references: 18556784
references: Environ Microbiol. 2011 Jun;13(6):1549-60
references: 21418497
references: Ann N Y Acad Sci. 2012 Apr;1253:16-36
references: 22524423
references: J Immunol. 2010 Jul 1;185(1):748-55
references: 20525894
references: Microbes Infect. 2009 Oct;11(12):988-94
references: 19631279
references: Infect Immun. 2012 Jul;80(7):2361-70
references: 22508861
references: J Biol Chem. 2003 Jul 4;278(27):24509-20
references: 12716884
references: Biochemistry. 1993 Mar 2;32(8):2003-12
references: 8448159
references: J Bacteriol. 2011 Aug;193(16):4238-49
references: 21642451
references: Infect Immun. 2006 May;74(5):2697-705
references: 16622206
references: J Bacteriol. 1991 Jan;173(2):618-26
references: 1987154
references: Clin Infect Dis. 2001 Apr 15;32(8):1201-6
references: 11283810
references: Infect Immun. 2009 Jun;77(6):2499-507
references: 19332531
references: Infect Immun. 2012 Nov;80(11):4014-26
references: 22949553
references: Proc Natl Acad Sci U S A. 2005 Jun 28;102(26):9247-52
references: 15956202
references: Proc Natl Acad Sci U S A. 2005 Nov 1;102(44):16043-8
references: 16230626
references: Nature. 2009 Apr 30;458(7242):1191-5
references: 19252480
references: Cell Microbiol. 2005 Apr;7(4):519-28
references: 15760452
references: J Biol Chem. 2012 Aug 24;287(35):29384-96
references: 22761430
references: J Invest Dermatol. 1990 Dec;95(6 Suppl):81S-84S
references: 1701813
references: J Biol Chem. 2009 Aug 7;284(32):21515-25
references: 19531474
references: Appl Environ Microbiol. 2005 Apr;71(4):1876-82
references: 15812015
references: Clin Infect Dis. 2011 Jul 1;53(1):26-32
references: 21653299
references: J Biol Chem. 2009 Nov 13;284(46):31982-91
references: 19759006
references: J Lipid Res. 2009 Mar;50(3):424-438
references: 18832773
references: Science. 2007 Jun 15;316(5831):1628-32
references: 17569868
references: J Biol Chem. 2010 May 21;285(21):15828-36
references: 20351099
references: Infect Immun. 2008 Oct;76(10):4431-8
references: 18644887
references: J Clin Microbiol. 2005 Jun;43(6):2771-81
references: 15956396
references: J Clin Invest. 2004 Dec;114(11):1659-65
references: 15578098
references: J Biol Chem. 2012 Jan 27;287(5):3326-36
references: 22158617
references: Biochemistry. 2007 Dec 18;46(50):14704-14
references: 18034462
references: Infect Immun. 2013 Feb;81(2):430-40
references: 23184526
references: Science. 1998 Dec 11;282(5396):2085-8
references: 9851930
references: Eur J Biochem. 1991 Jun 1;198(2):459-69
references: 2040305
references: Infect Immun. 2010 Mar;78(3):1229-38
references: 20038539
references: Immunobiology. 2004;209(1-2):199-207
references: 15481154
references: J Infect Dis. 1988 Mar;157(3):472-9
references: 3343522