A novel mouse model of Campylobacter jejuni gastroenteritis reveals key pro-inflammatory and tissue protective roles for Toll-like receptor signaling during infection.

Campylobacter jejuni is a major source of foodborne illness in the developed world, and a common cause of clinical gastroenteritis. Exactly how C. jejuni colonizes its host's intestines and causes disease is poorly understood. Although it causes severe diarrhea and gastroenteritis in humans, C....

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Autores principales:	Martin Stahl, Jenna Ries, Jenny Vermeulen, Hong Yang, Ho Pan Sham, Shauna M Crowley, Yuliya Badayeva, Stuart E Turvey, Erin C Gaynor, Xiaoxia Li, Bruce A Vallance
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/2ed7abe3073d429899f0a2250446147d
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spelling	oai:doaj.org-article:2ed7abe3073d429899f0a2250446147d2021-11-25T05:46:16ZA novel mouse model of Campylobacter jejuni gastroenteritis reveals key pro-inflammatory and tissue protective roles for Toll-like receptor signaling during infection.1553-73661553-737410.1371/journal.ppat.1004264https://doaj.org/article/2ed7abe3073d429899f0a2250446147d2014-07-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25033044/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Campylobacter jejuni is a major source of foodborne illness in the developed world, and a common cause of clinical gastroenteritis. Exactly how C. jejuni colonizes its host's intestines and causes disease is poorly understood. Although it causes severe diarrhea and gastroenteritis in humans, C. jejuni typically dwells as a commensal microbe within the intestines of most animals, including birds, where its colonization is asymptomatic. Pretreatment of C57BL/6 mice with the antibiotic vancomycin facilitated intestinal C. jejuni colonization, albeit with minimal pathology. In contrast, vancomycin pretreatment of mice deficient in SIGIRR (Sigirr(-/-)), a negative regulator of MyD88-dependent signaling led to heavy and widespread C. jejuni colonization, accompanied by severe gastroenteritis involving strongly elevated transcription of Th1/Th17 cytokines. C. jejuni heavily colonized the cecal and colonic crypts of Sigirr(-/-) mice, adhering to, as well as invading intestinal epithelial cells. This infectivity was dependent on established C. jejuni pathogenicity factors, capsular polysaccharides (kpsM) and motility/flagella (flaA). We also explored the basis for the inflammatory response elicited by C. jejuni in Sigirr(-/-) mice, focusing on the roles played by Toll-like receptors (TLR) 2 and 4, as these innate receptors were strongly stimulated by C. jejuni. Despite heavy colonization, Tlr4(-/-)/Sigirr(-/-) mice were largely unresponsive to infection by C. jejuni, whereas Tlr2(-/-)/Sigirr(-/-) mice developed exaggerated inflammation and pathology. This indicates that TLR4 signaling underlies the majority of the enteritis seen in this model, whereas TLR2 signaling had a protective role, acting to promote mucosal integrity. Furthermore, we found that loss of the C. jejuni capsule led to increased TLR4 activation and exaggerated inflammation and gastroenteritis. Together, these results validate the use of Sigirr(-/-) mice as an exciting and relevant animal model for studying the pathogenesis and innate immune responses to C. jejuni.Martin StahlJenna RiesJenny VermeulenHong YangHo Pan ShamShauna M CrowleyYuliya BadayevaStuart E TurveyErin C GaynorXiaoxia LiBruce A VallancePublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 10, Iss 7, p e1004264 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Martin Stahl Jenna Ries Jenny Vermeulen Hong Yang Ho Pan Sham Shauna M Crowley Yuliya Badayeva Stuart E Turvey Erin C Gaynor Xiaoxia Li Bruce A Vallance A novel mouse model of Campylobacter jejuni gastroenteritis reveals key pro-inflammatory and tissue protective roles for Toll-like receptor signaling during infection.
description	Campylobacter jejuni is a major source of foodborne illness in the developed world, and a common cause of clinical gastroenteritis. Exactly how C. jejuni colonizes its host's intestines and causes disease is poorly understood. Although it causes severe diarrhea and gastroenteritis in humans, C. jejuni typically dwells as a commensal microbe within the intestines of most animals, including birds, where its colonization is asymptomatic. Pretreatment of C57BL/6 mice with the antibiotic vancomycin facilitated intestinal C. jejuni colonization, albeit with minimal pathology. In contrast, vancomycin pretreatment of mice deficient in SIGIRR (Sigirr(-/-)), a negative regulator of MyD88-dependent signaling led to heavy and widespread C. jejuni colonization, accompanied by severe gastroenteritis involving strongly elevated transcription of Th1/Th17 cytokines. C. jejuni heavily colonized the cecal and colonic crypts of Sigirr(-/-) mice, adhering to, as well as invading intestinal epithelial cells. This infectivity was dependent on established C. jejuni pathogenicity factors, capsular polysaccharides (kpsM) and motility/flagella (flaA). We also explored the basis for the inflammatory response elicited by C. jejuni in Sigirr(-/-) mice, focusing on the roles played by Toll-like receptors (TLR) 2 and 4, as these innate receptors were strongly stimulated by C. jejuni. Despite heavy colonization, Tlr4(-/-)/Sigirr(-/-) mice were largely unresponsive to infection by C. jejuni, whereas Tlr2(-/-)/Sigirr(-/-) mice developed exaggerated inflammation and pathology. This indicates that TLR4 signaling underlies the majority of the enteritis seen in this model, whereas TLR2 signaling had a protective role, acting to promote mucosal integrity. Furthermore, we found that loss of the C. jejuni capsule led to increased TLR4 activation and exaggerated inflammation and gastroenteritis. Together, these results validate the use of Sigirr(-/-) mice as an exciting and relevant animal model for studying the pathogenesis and innate immune responses to C. jejuni.
format	article
author	Martin Stahl Jenna Ries Jenny Vermeulen Hong Yang Ho Pan Sham Shauna M Crowley Yuliya Badayeva Stuart E Turvey Erin C Gaynor Xiaoxia Li Bruce A Vallance
author_facet	Martin Stahl Jenna Ries Jenny Vermeulen Hong Yang Ho Pan Sham Shauna M Crowley Yuliya Badayeva Stuart E Turvey Erin C Gaynor Xiaoxia Li Bruce A Vallance
author_sort	Martin Stahl
title	A novel mouse model of Campylobacter jejuni gastroenteritis reveals key pro-inflammatory and tissue protective roles for Toll-like receptor signaling during infection.
title_short	A novel mouse model of Campylobacter jejuni gastroenteritis reveals key pro-inflammatory and tissue protective roles for Toll-like receptor signaling during infection.
title_full	A novel mouse model of Campylobacter jejuni gastroenteritis reveals key pro-inflammatory and tissue protective roles for Toll-like receptor signaling during infection.
title_fullStr	A novel mouse model of Campylobacter jejuni gastroenteritis reveals key pro-inflammatory and tissue protective roles for Toll-like receptor signaling during infection.
title_full_unstemmed	A novel mouse model of Campylobacter jejuni gastroenteritis reveals key pro-inflammatory and tissue protective roles for Toll-like receptor signaling during infection.
title_sort	novel mouse model of campylobacter jejuni gastroenteritis reveals key pro-inflammatory and tissue protective roles for toll-like receptor signaling during infection.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/2ed7abe3073d429899f0a2250446147d
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A novel mouse model of Campylobacter jejuni gastroenteritis reveals key pro-inflammatory and tissue protective roles for Toll-like receptor signaling during infection.

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