Pseudaminic acid on Campylobacter jejuni flagella modulates dendritic cell IL-10 expression via Siglec-10 receptor: a novel flagellin-host interaction.
BACKGROUND
Campylobacter jejuni is a leading cause of bacterial gastroenteritis worldwide. At present the identity of host-pathogen interactions that promote successful bacterial colonisation remain ill defined. Herein, we aimed to investigate C. jejuni-mediated effects on dendritic cell (DC) immunity.


RESULTS
We found C. jejuni to be a potent inducer of human and murine DC interleukin 10 (IL-10) in vitro, a cellular event that was MyD88- and p38 MAPK-signalling dependent. Utilizing a series of C. jejuni isogenic mutants we found the major flagellin protein, FlaA, modulated IL-10 expression, an intriguing observation as C. jejuni FlaA is not a TLR5 agonist. Further analysis revealed pseudaminic acid residues on the flagella contributed to DC IL-10 expression. We identified the ability of both viable C. jejuni and purified flagellum to bind to Siglec-10, an immune-modulatory receptor. In vitro infection of Siglec-10 overexpressing cells resulted in increased IL-10 expression in a p38-dependent manner. Detection of Siglec-10 on intestinal CD11c(+) CD103(+) DCs added further credence to the notion that this novel interaction may contribute to immune outcome during human infection.


CONCLUSIONS
We propose that unlike the Salmonella Typhimurium flagella-TLR5 driven pro-inflammatory axis, C. jejuni flagella instead promote an anti-inflammatory axis via glycan-Siglec-10 engagement.
Infectious Diseases and Microbiology Unit, Institute of Child Health, University College London.
Holly N
HN
Stephenson
Department of Pathogen Molecular Biology, London School of Hygiene and Tropical Medicine.
Dominic C
DC
Mills
Infectious Diseases and Microbiology Unit, Institute of Child Health, University College London.
Hannah
H
Jones
Infectious Diseases and Microbiology Unit, Institute of Child Health, University College London.
Enea
E
Milioris
Infectious Diseases and Microbiology Unit, Institute of Child Health, University College London.
Alastair
A
Copland
Department of Pathogen Molecular Biology, London School of Hygiene and Tropical Medicine.
Nick
N
Dorrell
Department of Pathogen Molecular Biology, London School of Hygiene and Tropical Medicine.
Brendan W
BW
Wren
College of Life Sciences, University of Dundee.
Paul R
PR
Crocker
Rayne Institute, University College London, United Kingdom Navarrabiomed-Fundacion Miguel Servet, Pamplona, Navarra, Spain.
David
D
Escors
Infectious Diseases and Microbiology Unit, Institute of Child Health, University College London.
Mona
M
Bajaj-Elliott
D000818:Animals; D002169:Campylobacter Infections / Q000382:microbiology / Q000503:physiopathology*; D016123:Campylobacter jejuni / Q000502:physiology*; D003713:Dendritic Cells / Q000378:metabolism* / Q000502:physiology; D005407:Flagella / Q000502:physiology*; D054884:Host-Pathogen Interactions / Q000502:physiology*; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis / Q000502:physiology*; D037102:Lectins / Q000502:physiology*; D008810:Mice, Inbred C57BL; D011956:Receptors, Cell Surface / Q000502:physiology*; D013400:Sugar Acids / Q000378:metabolism*
C513444:5,7-diacetamido-3,5,7,9-tetradeoxynonulosonic acid; D037102:Lectins; D011956:Receptors, Cell Surface; C426228:SIGLEC10 protein, human; D013400:Sugar Acids; D016753:Interleukin-10
Campylobacter jejuni; IL-10; Siglec-10; dendritic cells; immune modulation; p38