Pseudaminic acid on Campylobacter jejuni flagella modulates dendritic cell IL-10 expression via Siglec-10 receptor: a novel flagellin-host interaction

Holly N. Stephenson; Dominic C. Mills; Hannah Jones; Enea Milioris; Alastair Copland; Nick Dorrell; Brendan W. Wren; Paul R. Crocker; David Escors; Mona Bajaj-Elliott

doi:10.1093/infdis/jiu287

Pseudaminic acid on Campylobacter jejuni flagella modulates dendritic cell IL-10 expression via Siglec-10 receptor: a novel flagellin-host interaction

Holly N. Stephenson, Dominic C. Mills, Hannah Jones, Enea Milioris, Alastair Copland, Nick Dorrell, Brendan W. Wren, Paul R. Crocker, David Escors, Mona Bajaj-Elliott (Lead / Corresponding author)

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Abstract

INTRODUCTION: 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.

Original language	English
Pages (from-to)	1487-1498
Number of pages	12
Journal	Journal of Infectious Diseases
Volume	210
Issue number	9
DOIs	https://doi.org/10.1093/infdis/jiu287
Publication status	Published - 1 Nov 2014

Keywords

Animals
Campylobacter Infections
Campylobacter jejuni
Dendritic Cells
Flagella
Host-Pathogen Interactions
Humans
Interleukin-10
Lectins
Mice, Inbred C57BL
Receptors, Cell Surface
Sugar Acids

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10.1093/infdis/jiu287

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© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Final published version, 903 KBLicence: CC BY

http://jid.oxfordjournals.org/

Aref#d: 19149. Role of Siglecs in Disease (Senior Research Fellowship)
Crocker, P. (Investigator)
1/11/07 → 30/04/13
Project: Research

Cite this

Stephenson, H. N., Mills, D. C., Jones, H., Milioris, E., Copland, A., Dorrell, N., Wren, B. W., Crocker, P. R., Escors, D., & Bajaj-Elliott, M. (2014). Pseudaminic acid on Campylobacter jejuni flagella modulates dendritic cell IL-10 expression via Siglec-10 receptor: a novel flagellin-host interaction. Journal of Infectious Diseases, 210(9), 1487-1498. https://doi.org/10.1093/infdis/jiu287

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title = "Pseudaminic acid on Campylobacter jejuni flagella modulates dendritic cell IL-10 expression via Siglec-10 receptor: a novel flagellin-host interaction",

abstract = "INTRODUCTION: 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.",

keywords = "Animals, Campylobacter Infections, Campylobacter jejuni, Dendritic Cells, Flagella, Host-Pathogen Interactions, Humans, Interleukin-10, Lectins, Mice, Inbred C57BL, Receptors, Cell Surface, Sugar Acids",

author = "Stephenson, {Holly N.} and Mills, {Dominic C.} and Hannah Jones and Enea Milioris and Alastair Copland and Nick Dorrell and Wren, {Brendan W.} and Crocker, {Paul R.} and David Escors and Mona Bajaj-Elliott",

note = "{\textcopyright} The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.",

year = "2014",

month = nov,

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doi = "10.1093/infdis/jiu287",

language = "English",

volume = "210",

pages = "1487--1498",

journal = "Journal of Infectious Diseases",

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Stephenson, HN, Mills, DC, Jones, H, Milioris, E, Copland, A, Dorrell, N, Wren, BW, Crocker, PR, Escors, D & Bajaj-Elliott, M 2014, 'Pseudaminic acid on Campylobacter jejuni flagella modulates dendritic cell IL-10 expression via Siglec-10 receptor: a novel flagellin-host interaction', Journal of Infectious Diseases, vol. 210, no. 9, pp. 1487-1498. https://doi.org/10.1093/infdis/jiu287

TY - JOUR

T1 - Pseudaminic acid on Campylobacter jejuni flagella modulates dendritic cell IL-10 expression via Siglec-10 receptor

T2 - a novel flagellin-host interaction

AU - Stephenson, Holly N.

AU - Mills, Dominic C.

AU - Jones, Hannah

AU - Milioris, Enea

AU - Copland, Alastair

AU - Dorrell, Nick

AU - Wren, Brendan W.

AU - Crocker, Paul R.

AU - Escors, David

AU - Bajaj-Elliott, Mona

N1 - © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

PY - 2014/11/1

Y1 - 2014/11/1

N2 - INTRODUCTION: 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.

AB - INTRODUCTION: 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.

KW - Animals

KW - Campylobacter Infections

KW - Campylobacter jejuni

KW - Dendritic Cells

KW - Flagella

KW - Host-Pathogen Interactions

KW - Humans

KW - Interleukin-10

KW - Lectins

KW - Mice, Inbred C57BL

KW - Receptors, Cell Surface

KW - Sugar Acids

U2 - 10.1093/infdis/jiu287

DO - 10.1093/infdis/jiu287

M3 - Article

C2 - 24823621

SN - 0022-1899

VL - 210

SP - 1487

EP - 1498

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

IS - 9

ER -

Pseudaminic acid on Campylobacter jejuni flagella modulates dendritic cell IL-10 expression via Siglec-10 receptor: a novel flagellin-host interaction

Abstract

Keywords

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Aref#d: 19149. Role of Siglecs in Disease (Senior Research Fellowship)

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