The role of interleukin-10 (IL-10) in the regulation of innate immunity in the domestic chicken
Lead Research Organisation:
Royal Veterinary College
Department Name: Pathology and Pathogen Biology
Abstract
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Technical Summary
The challenge to the poultry industry in selective breeding for natural resistance is to identify quantitative markers that identify individuals with superior performance in the presence of infection. Our current BBSRC ARC funded work has revealed that circulating IL-10 could provide a biomarker to identify birds that are resilient when challenged with Eimeria spp. In this study we will explore the genetic control of IL-10 production, and the consequences of selection for low IL-10 production. We will assay circulating IL-10 in the response of large cohorts of commercial broiler and layer birds to Eimeria challenge, alone or in combination with other enteric pathogens (e.g. Campylobacter jejuni, Clostridium perfringens), and apply genome-wide association (GWA) using high density SNP chips and/or whole genome resequencing to identify cis and trans-acting variants that control circulating IL-10 and other indices of the response to challenge. To test the direct role of IL-10, we will breed variant IL-10 alleles to homozygosity, produce IL-10 knockouts by gene-editing, and examine the effect of neutralising IL-10 antibodies on the response to infection.
Planned Impact
Sustainability of the UK and international poultry industries face numerous challenges including pathogen resistance to control and withdrawal of prophylactic/therapeutic antibiotics in an attempt to tighten biosecurity of food destined for human consumption. Our project seeks to provide an intellectual foundation, and possible tools, toward efforts to breed lines of genetically disease resistant and resilient birds. These will include a better understanding of host-pathogen interactions vital to the investigation of new and effective measures of disease control and determination of the implications of selecting for specific traits using newly identified biomarkers to ensure economic goals and animal welfare are not compromised. Outcomes will assist in increasing competitiveness in international markets for the supply of safe, healthy and comparatively cheap food to an ever-increasing world population.
1. The poultry production industry
Eimeria spp, (cause of coccidiosis), cost the international poultry industry approximately $3.5bn (£800M in the UK) per annum, chiefly through loss in production and the cost of prophylaxis. Clostridium perfringens can cause necrotic enteritis (in coinfection with Eimeria). Campylobacter jejuni is the leading cause of foodborne enteritis in the developed world, with poultry products a major source. Addressing 'animal health and welfare, and genetics and genomics for improved production and disease resistance', the work proposed is directly relevant to BBSRC's Strategic Research Priority 1.
2. The UK poultry breeding industry
The structure of the UK poultry industry is such that collaboration with the major breeding companies will provide a cascade of breeding developments, 'ensuring exchange of knowledge between the science base and industry through effective networking'. Understanding the relevance of IL-10 to enteric disease, and thus productivity and welfare, of chickens can provide a major new biomarker to inform breeding strategies.
3. The UK animal health industry
Understanding the impact of IL-10, and the consequences of Eimeria infection, on immune responses to enteric pathogens and vaccination can impact on current and future vaccine application ('Understanding variation in vaccine responsiveness, immuno-competence at different developmental stages and disease outcomes').
4. Animal welfare
The effective reduction of disease as a result of improved breeding supports the Five Freedoms implicit to animal welfare as set out by the Farm Animal Welfare Council.
5. General public and the environment
Increased efficiency in poultry production will raise poultry product availability at a lower cost for the consumer, contributing to improved food security. Consequences of improved disease resistance include a reduction in the requirement for prophylactic chemotherapy, reducing drug consumption and the risk of contamination to the food chain and the environment. While Eimeria is not transferrable to humans, in 2004, Campylobacter jejuni and Clostridium perfringens (together with Salmonella spp) were responsible for in excess of 350,000 reported cases of food poisoning in the UK.
6. Skills, knowledge and training
The multidisciplinary nature of this project will provide opportunities for broad training to all staff, in addition to other members and students of each host institution ('strengthen the research community in the areas of disease and pest resistance of farmed animals through interdisciplinary research and the provision of training'). Access to IL-10 deficient and knockout birds will be a major international resource through NARF.
7. International development
Eimerian parasites impose serious costs on animal production in developing counties. Translating 'high quality, innovative, strategic research within UK universities and institutes to improve the resistance of farmed animals to pest and disease organisms' can improve economic income and alleviate poverty.
1. The poultry production industry
Eimeria spp, (cause of coccidiosis), cost the international poultry industry approximately $3.5bn (£800M in the UK) per annum, chiefly through loss in production and the cost of prophylaxis. Clostridium perfringens can cause necrotic enteritis (in coinfection with Eimeria). Campylobacter jejuni is the leading cause of foodborne enteritis in the developed world, with poultry products a major source. Addressing 'animal health and welfare, and genetics and genomics for improved production and disease resistance', the work proposed is directly relevant to BBSRC's Strategic Research Priority 1.
2. The UK poultry breeding industry
The structure of the UK poultry industry is such that collaboration with the major breeding companies will provide a cascade of breeding developments, 'ensuring exchange of knowledge between the science base and industry through effective networking'. Understanding the relevance of IL-10 to enteric disease, and thus productivity and welfare, of chickens can provide a major new biomarker to inform breeding strategies.
3. The UK animal health industry
Understanding the impact of IL-10, and the consequences of Eimeria infection, on immune responses to enteric pathogens and vaccination can impact on current and future vaccine application ('Understanding variation in vaccine responsiveness, immuno-competence at different developmental stages and disease outcomes').
4. Animal welfare
The effective reduction of disease as a result of improved breeding supports the Five Freedoms implicit to animal welfare as set out by the Farm Animal Welfare Council.
5. General public and the environment
Increased efficiency in poultry production will raise poultry product availability at a lower cost for the consumer, contributing to improved food security. Consequences of improved disease resistance include a reduction in the requirement for prophylactic chemotherapy, reducing drug consumption and the risk of contamination to the food chain and the environment. While Eimeria is not transferrable to humans, in 2004, Campylobacter jejuni and Clostridium perfringens (together with Salmonella spp) were responsible for in excess of 350,000 reported cases of food poisoning in the UK.
6. Skills, knowledge and training
The multidisciplinary nature of this project will provide opportunities for broad training to all staff, in addition to other members and students of each host institution ('strengthen the research community in the areas of disease and pest resistance of farmed animals through interdisciplinary research and the provision of training'). Access to IL-10 deficient and knockout birds will be a major international resource through NARF.
7. International development
Eimerian parasites impose serious costs on animal production in developing counties. Translating 'high quality, innovative, strategic research within UK universities and institutes to improve the resistance of farmed animals to pest and disease organisms' can improve economic income and alleviate poverty.
People |
ORCID iD |
Damer Blake (Principal Investigator) | |
Fiona Tomley (Co-Investigator) |
Publications
Soutter F
(2020)
Poultry Coccidiosis: Design and Interpretation of Vaccine Studies.
in Frontiers in veterinary science
Soutter F
(2021)
Impact of Eimeria tenella Oocyst Dose on Parasite Replication, Lesion Score and Cytokine Transcription in the Caeca in Three Breeds of Commercial Layer Chickens.
in Frontiers in veterinary science
Williams J
(2022)
Differential expression of microRNAs in the caecal content and faeces of broiler chickens experimentally infected with Eimeria.
in Avian pathology : journal of the W.V.P.A
Description | Initially we confirmed that all traits targeted in the project were polymorphic and displayed sufficient variation to be used in genetic mapping studies. Subsequently, we have phenotyped several large cohorts of Light Sussex chickens and received genotyping data that will permit analysis. We have now completed all in vivo studies in commercial Cobb500 chickens, collecting immediately accessible phenotypes (body weight gain, lesion score) at the time of the studies. The COVID-19 pandemic initially prevented us from completing molecular analyses (parasite replication, cytokine transcription), but these are now complete and up to date, benefitting from a no cost extension. Our partners (University of Edinburgh/Roslin Institute) have also received an extension, permitting genome wide genetic analysis to be undertaken with results anticipated soon. Finally, we undertook a series of infection studies to assess the consequences of genetic disruption to the interleukin 10 locus on Eimeria infection. |
Exploitation Route | Information including genetic markers associated with resistance to Eimeria infection, and knowledge defining the value of IL-10 as a marker of intestinal inflammation, can be used by breeding companies to improve chicken health and welfare. the information can also be used by the animal health/veterinary field to improve health and welfare. The work is applicable to all pathogens which can cause disease in the gastrointestinal tract. |
Sectors | Agriculture Food and Drink |
Description | This work has supported creation and understanding of a new genetic knockout chicken line. Phenotyping the new line has informed on impact of specific immune responses on parasite infection with wider utility for understanding the mechanisms and consequences of anti-pathogen vaccination in chickens. The work has also supported development of PhD student studies. |
First Year Of Impact | 2022 |
Sector | Agriculture, Food and Drink,Education |
Description | Phibro seminar 2 |
Geographic Reach | Asia |
Policy Influence Type | Influenced training of practitioners or researchers |
Impact | Improved use of drugs in livestock production (antimicrobial and antiparasitic) |
Description | Phytobiotics 2 |
Geographic Reach | Europe |
Policy Influence Type | Influenced training of practitioners or researchers |
Impact | Improved use of drugs in livestock production (antimicrobial and antiparasitic) |
Description | USDA meeting |
Geographic Reach | North America |
Policy Influence Type | Contribution to new or Improved professional practice |
Description | GCRF One Health Poultry Hub |
Amount | £17,718,608 (GBP) |
Funding ID | BB/S011269/1 |
Organisation | Royal Veterinary College (RVC) |
Sector | Academic/University |
Country | United Kingdom |
Start | 03/2019 |
End | 02/2025 |
Description | Houghton Trust Small Research Grants Scheme |
Amount | £5,000 (GBP) |
Organisation | Royal Veterinary College (RVC) |
Sector | Academic/University |
Country | United Kingdom |
Start | 11/2018 |
End | 09/2019 |
Description | The association of GPR35 with chicken intestinal dysbiosis |
Amount | £1,510 (GBP) |
Funding ID | HT/VSG/23/01 |
Organisation | The Houghton Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 06/2023 |
End | 08/2023 |
Description | Understanding the contribution of host genetics, intestinal structure and microbiome diversity to gut health in broiler chickens |
Amount | £186,324 (GBP) |
Funding ID | 2548047 |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 08/2021 |
End | 09/2025 |
Description | Understanding the contribution of host genetics, intestinal structure and microbiome diversity to gut health in broiler chickens. LIDo iCASE DTP PhD Studentship |
Amount | £204,000 (GBP) |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 09/2021 |
End | 09/2025 |
Description | Yeast-based vaccine platform as a tool to target avian M-cells: an approach for tackling infectious intestinal diseases Yeast-based vaccine platform as a tool to target avian M-cells: an approach for tackling infectious intestinal diseases in chickens |
Amount | £10,162 (GBP) |
Funding ID | HT/SPRG/23/05 |
Organisation | The Houghton Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 08/2023 |
End | 08/2024 |
Description | University of Thessaloniki - impact of Eimeria on chicken performance and alternatives for control |
Organisation | Aristotle University of Thessaloniki |
Country | Greece |
Sector | Academic/University |
PI Contribution | Provision of Eimeria species parasites and expert knowledge related to doses and measures of parasitaemia. |
Collaborator Contribution | In vivo studies exploring the impact of a range of novel controls |
Impact | DOI: 10.3389/fvets.2020.00420. DOI: 10.3390/life12111783. |
Start Year | 2020 |
Description | 4th Annual RVC Research Highlights Day |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Postgraduate students |
Results and Impact | Postdoctoral presentation to reearch highlights day, promoting the work and providing an opportunity for career development. |
Year(s) Of Engagement Activity | 2018 |
Description | Avian Infectious Diseases 2021. Microbiology Society online conference |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Invited conference presentation exploring progress towards development of novel anticoccidial vaccines |
Year(s) Of Engagement Activity | 2021 |
Description | Avian Pathology Lecture Award at the XXIInd World Veterinary Poultry Association Congress |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Award presentation to an audience of ~800, primarily veterinarians as well as animal health and breeding company representatives. Discussions and proposals for collaboration followed, plus new links with industry. |
Year(s) Of Engagement Activity | 2023 |
URL | https://www.houghtontrust.org.uk/sponsored-lectures |
Description | Britsh Poultry Council |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Industry/Business |
Results and Impact | Presented to the BPC and engaged in discussion on intestinal dysbiosis, impact of Eimeria and microbiomes. |
Year(s) Of Engagement Activity | 2019 |
Description | DISCONTOOLS Coccidiosis (Poultry) |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Working group and report published updating understanding of the impact and control of coccidiosis |
Year(s) Of Engagement Activity | 2023 |
URL | https://www.discontools.eu/database/68-coccidiosis.html |
Description | European Coccidiosis Discussion Group (ECDG) |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Industry/academia networking event including presentations and discussions around ongoing RVC projects. |
Year(s) Of Engagement Activity | 2018 |
Description | Hipra World Virtual Poultry Congress |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Industry/Business |
Results and Impact | Invited presentation to an industry symposium, focusing on microbiology and immunology of chickens with relevance to health and welfare. |
Year(s) Of Engagement Activity | 2021 |
Description | Industry advisory board meeting on coccidiosis |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Industry/Business |
Results and Impact | Two day advisory board meeting with industry representatives focused on control of coccidiosis in chickens and approaches to fast track new vaccines. Included a panel of international (European + USA) representatives. |
Year(s) Of Engagement Activity | 2022 |
Description | Invited presentation at the Veterinary Research Group |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | Invited presentation to Veterinary Research Club. Online delivery to ~25 people. |
Year(s) Of Engagement Activity | 2023 |
Description | Plenary presentation - Eimeriana Avia |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | ~200 delegates at an international conference that primarily drew practitioners and businesses from Eastern Europe. Considerable discussion around microbiomes, chicken genetics and the potential to modulate the microbiome and immune responses to improve productivity and welfare. |
Year(s) Of Engagement Activity | 2020 |
Description | Poster presentation - Association for Veterinary Teaching and Research Work (AVTRW) 76th Annual Conference |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Postgraduate students |
Results and Impact | Maria Vasilogianni presented a poster "Understanding how the expression of IL-10 affects chicken intestinal morphology and microbiome diversity following Eimeria tenella infection" at the 76th Annual Association for Veterinary Teaching and Research Work (AVTRW) Conference to an audience of ~60 people (primarily postgraduate students and early career researchers). Discussion after the event supported development of analysis pipelines. |
Year(s) Of Engagement Activity | 2022 |
Description | Poultry Diseases Group meeting - 2022 |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | Discussed project progress and relevance to UK poultry producers at the Poultry Disease Group meeting, a workshop linking veterinary practitioners, industry representatives and academics. |
Year(s) Of Engagement Activity | 2022 |
Description | Poultry Health Course |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Presenting the pathology and control of Eimeria, including interactions with host genetics and the enteric microflora. |
Year(s) Of Engagement Activity | 2017,2018 |
Description | Presentation at industry conference (Huvepharma) |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Invited presentation to industry professionals at Huvepharma workshop in Bulgaria. An audience of ~250, primarily veterinarians as well as animal health and breeding company representatives. Discussions and proposals for collaboration followed. |
Year(s) Of Engagement Activity | 2023 |
Description | Study workshop at the Norwegian Veterinary Institute |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Postgraduate students |
Results and Impact | Invited presentation to the Norwegian Veterinary Institute and working group participation to explore improved control of Eimeria. |
Year(s) Of Engagement Activity | 2023 |
Description | University of Kent invited talk |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Undergraduate students |
Results and Impact | ~80 people attended an invited talk in the University of Kent external seminar series. A series of questions were addressed after the talk, followed by 1-2-1 discussions on possible projects and grant applications. focused on the microbiome, as well as aspects of host susceptibility and genetics. |
Year(s) Of Engagement Activity | 2019 |
Description | Webinar |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | Pathobiology and current vaccine research strategies for control of chicken coccidia. Recent developments in pathobiology and diagnosis of animal and poultry diseases - A new prospective approach. International Webinar. Tamil Nadu Veterinary and Animal Sciences University (TANUVAS) (~300 delegates). 15th October 2020 |
Year(s) Of Engagement Activity | 2020 |
Description | Webinar |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Strategies to control coccidiosis in poultry: why, what and how?. Defeating biotic stressors to safeguard poultry production, health and food safety. International Webinar. Tamil Nadu Veterinary and Animal Sciences University (TANUVAS) (~400 delegates). 27th November 2020 |
Year(s) Of Engagement Activity | 2020 |
Description | Webinar |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Industry/Business |
Results and Impact | Eimeria and anticoccidial vaccines. Phytobiotics webinar (228 delegates). 4th March 2021. Asia and Australia |
Year(s) Of Engagement Activity | 2021 |
Description | Webinar |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Industry/Business |
Results and Impact | Eimeria and anticoccidial vaccines. Phytobiotics webinar (58 delegates). 27th January 2021. |
Year(s) Of Engagement Activity | 2021 |
Description | World Veterinary Poultry Association CPD day |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | ~150 delegates attended a CPD training day organised by the World Veterinary Poultry Association, Malaysia branch. The day featured a series of talks from academics, industry representatives and veterinarians. Two talks decribing BBSRC funded studies were presented, focusing on (i) occurrence and genetic diversity of Eimeria, and (ii) the poultry enteric microbiome and links to chicken genetics. |
Year(s) Of Engagement Activity | 2020 |