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Host Pathogen responses of chicken cells in vitro and in vivo to a diverse population of Campylobacter strains / Daniel A. John

Swansea University Author: Daniel A. John

DOI (Published version): 10.23889/Suthesis.50200

Abstract

Campylobacter is the leading cause of bacterial food-borne diarrheal disease worldwide, with the bacteria being pathogens in humans and chickens. There are differences in the mechanistic understanding between Campylobacter strains, due, in part, to genomic and phenotypic strain diversity, which lead...

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Published: 2018
Institution: Swansea University
Degree level: Doctoral
Degree name: Ph.D
URI: https://cronfa.swan.ac.uk/Record/cronfa50200
first_indexed 2019-05-09T20:01:10Z
last_indexed 2025-04-05T03:41:58Z
id cronfa50200
recordtype RisThesis
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This study aimed to understand underlying infection biology in host-pathogen interactions between populations of Campylobacter and the chicken host. A collection of Campylobacter jejuni strains were used to investigate the genotypic and phenotypic differences which yielded a diverse pan-geome of 2715 genes with genome wide association studies uncovering genes related to flagella assocaited with strains isolated from both humans and chickens. The C. jejuni strains were then used with a new commercially available chicken cell line to investigate the chicken systems with host responses measured in comparison to human systems. The pathogenic diversity of C. jejuni was measured through their inflammatory, cytotoxicity, adhesion, invasion and signalling responses in a high-throughput model using avian and human intestinal epithelial cells. C. jejuni induced IL-8 and CXCLi1/2 in human and avian epithelial cells, respectively, in a MAP kinase-dependent manner. In contrast, IL-10 responses in both cell types were PI 3-kinase/Akt-dependent. C. jejuni strains showed diverse levels of invasion with high invasion dependent on MAP kinase signaling in both cell lines. C. jejuni induced diverse cytotoxic responses in both cell lines with cdt-positive isolates showing significantly higher toxicity. Blockade of endocytic pathways suggested that invasion by C. jejuni was clathrin- and dynamin-dependent but caveolae- independent in both cells. In contrast, IL-8 (and CXCLi1/2) production was dependent on clathrin, dynamin, and caveolae. Strong correlations were found between IL-8 with invasion and toxicity responses with GWAS being able to associated genes to expression of IL-8,-10 and level of invasion. Campylobacter strains were isolated from the caeca, ileum and liver and a pan-genome created with GWAS analysis discovering genes relating to iron transport and heat shock proteins in strains from the liver. Subsequently, caecal tonsils were extracted from chickens uninfected and chickens infected with a cocktail of six Campylobacter strains with a Campylobacter effect found where infected chickens produced significantly higher Th1, Th2 and Th17 cytokines. The work in this thesis contributes invaluable knowledge on the chicken innate immune system in response to Campylobacter and how similar host defence pathways to humans are utlised. The diversity found strongly indicates that a &#x2018;one strain fits all&#x2019; approach to in vitro and in vivo experimental infections may not give accurate results on Campylobacter pathogenesis. 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spelling 2025-04-04T09:39:49.4573852 v2 50200 2019-05-02 Host Pathogen responses of chicken cells in vitro and in vivo to a diverse population of Campylobacter strains 6420df4866142d2c5823d7d759a50a94 NULL Daniel A. John Daniel A. John true true 2019-05-02 Campylobacter is the leading cause of bacterial food-borne diarrheal disease worldwide, with the bacteria being pathogens in humans and chickens. There are differences in the mechanistic understanding between Campylobacter strains, due, in part, to genomic and phenotypic strain diversity, which leads to inconsistent findings. This study aimed to understand underlying infection biology in host-pathogen interactions between populations of Campylobacter and the chicken host. A collection of Campylobacter jejuni strains were used to investigate the genotypic and phenotypic differences which yielded a diverse pan-geome of 2715 genes with genome wide association studies uncovering genes related to flagella assocaited with strains isolated from both humans and chickens. The C. jejuni strains were then used with a new commercially available chicken cell line to investigate the chicken systems with host responses measured in comparison to human systems. The pathogenic diversity of C. jejuni was measured through their inflammatory, cytotoxicity, adhesion, invasion and signalling responses in a high-throughput model using avian and human intestinal epithelial cells. C. jejuni induced IL-8 and CXCLi1/2 in human and avian epithelial cells, respectively, in a MAP kinase-dependent manner. In contrast, IL-10 responses in both cell types were PI 3-kinase/Akt-dependent. C. jejuni strains showed diverse levels of invasion with high invasion dependent on MAP kinase signaling in both cell lines. C. jejuni induced diverse cytotoxic responses in both cell lines with cdt-positive isolates showing significantly higher toxicity. Blockade of endocytic pathways suggested that invasion by C. jejuni was clathrin- and dynamin-dependent but caveolae- independent in both cells. In contrast, IL-8 (and CXCLi1/2) production was dependent on clathrin, dynamin, and caveolae. Strong correlations were found between IL-8 with invasion and toxicity responses with GWAS being able to associated genes to expression of IL-8,-10 and level of invasion. Campylobacter strains were isolated from the caeca, ileum and liver and a pan-genome created with GWAS analysis discovering genes relating to iron transport and heat shock proteins in strains from the liver. Subsequently, caecal tonsils were extracted from chickens uninfected and chickens infected with a cocktail of six Campylobacter strains with a Campylobacter effect found where infected chickens produced significantly higher Th1, Th2 and Th17 cytokines. The work in this thesis contributes invaluable knowledge on the chicken innate immune system in response to Campylobacter and how similar host defence pathways to humans are utlised. The diversity found strongly indicates that a ‘one strain fits all’ approach to in vitro and in vivo experimental infections may not give accurate results on Campylobacter pathogenesis. Campylobacter isolates can use host immune responses to its advantage and to move from the gut of chickens to infect edible tissues such as the liver. E-Thesis Microbiology, Host pathogen responses 31 12 2018 2018-12-31 10.23889/Suthesis.50200 COLLEGE NANME Swansea University Medical School COLLEGE CODE Swansea University Doctoral Ph.D Not Required 2025-04-04T09:39:49.4573852 2019-05-02T10:56:23.9896896 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Biomedical Science Daniel A. John NULL 1 0050200-02052019110640.pdf John_Daniel_A_PhD_Final_Thesis_Redacted_Signatureonly.pdf 2019-05-02T11:06:40.6870000 Output 5644062 application/pdf Redacted version - open access true 2019-11-01T00:00:00.0000000 true
title Host Pathogen responses of chicken cells in vitro and in vivo to a diverse population of Campylobacter strains
spellingShingle Host Pathogen responses of chicken cells in vitro and in vivo to a diverse population of Campylobacter strains
Daniel A. John
title_short Host Pathogen responses of chicken cells in vitro and in vivo to a diverse population of Campylobacter strains
title_full Host Pathogen responses of chicken cells in vitro and in vivo to a diverse population of Campylobacter strains
title_fullStr Host Pathogen responses of chicken cells in vitro and in vivo to a diverse population of Campylobacter strains
title_full_unstemmed Host Pathogen responses of chicken cells in vitro and in vivo to a diverse population of Campylobacter strains
title_sort Host Pathogen responses of chicken cells in vitro and in vivo to a diverse population of Campylobacter strains
author_id_str_mv 6420df4866142d2c5823d7d759a50a94
author_id_fullname_str_mv 6420df4866142d2c5823d7d759a50a94_***_Daniel A. John
author Daniel A. John
author2 Daniel A. John
format E-Thesis
publishDate 2018
institution Swansea University
doi_str_mv 10.23889/Suthesis.50200
college_str Faculty of Medicine, Health and Life Sciences
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hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Biomedical Science{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Biomedical Science
document_store_str 1
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description Campylobacter is the leading cause of bacterial food-borne diarrheal disease worldwide, with the bacteria being pathogens in humans and chickens. There are differences in the mechanistic understanding between Campylobacter strains, due, in part, to genomic and phenotypic strain diversity, which leads to inconsistent findings. This study aimed to understand underlying infection biology in host-pathogen interactions between populations of Campylobacter and the chicken host. A collection of Campylobacter jejuni strains were used to investigate the genotypic and phenotypic differences which yielded a diverse pan-geome of 2715 genes with genome wide association studies uncovering genes related to flagella assocaited with strains isolated from both humans and chickens. The C. jejuni strains were then used with a new commercially available chicken cell line to investigate the chicken systems with host responses measured in comparison to human systems. The pathogenic diversity of C. jejuni was measured through their inflammatory, cytotoxicity, adhesion, invasion and signalling responses in a high-throughput model using avian and human intestinal epithelial cells. C. jejuni induced IL-8 and CXCLi1/2 in human and avian epithelial cells, respectively, in a MAP kinase-dependent manner. In contrast, IL-10 responses in both cell types were PI 3-kinase/Akt-dependent. C. jejuni strains showed diverse levels of invasion with high invasion dependent on MAP kinase signaling in both cell lines. C. jejuni induced diverse cytotoxic responses in both cell lines with cdt-positive isolates showing significantly higher toxicity. Blockade of endocytic pathways suggested that invasion by C. jejuni was clathrin- and dynamin-dependent but caveolae- independent in both cells. In contrast, IL-8 (and CXCLi1/2) production was dependent on clathrin, dynamin, and caveolae. Strong correlations were found between IL-8 with invasion and toxicity responses with GWAS being able to associated genes to expression of IL-8,-10 and level of invasion. Campylobacter strains were isolated from the caeca, ileum and liver and a pan-genome created with GWAS analysis discovering genes relating to iron transport and heat shock proteins in strains from the liver. Subsequently, caecal tonsils were extracted from chickens uninfected and chickens infected with a cocktail of six Campylobacter strains with a Campylobacter effect found where infected chickens produced significantly higher Th1, Th2 and Th17 cytokines. The work in this thesis contributes invaluable knowledge on the chicken innate immune system in response to Campylobacter and how similar host defence pathways to humans are utlised. The diversity found strongly indicates that a ‘one strain fits all’ approach to in vitro and in vivo experimental infections may not give accurate results on Campylobacter pathogenesis. Campylobacter isolates can use host immune responses to its advantage and to move from the gut of chickens to infect edible tissues such as the liver.
published_date 2018-12-31T04:46:58Z
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