title: An explicit immunogenetic model of gastrointestinal nematode infection in sheep.
abstract: Gastrointestinal nematodes are a global cause of disease and death in humans, wildlife and livestock. Livestock infection has historically been controlled with anthelmintic drugs, but the development of resistance means that alternative controls are needed. The most promising alternatives are vaccination, nutritional supplementation and selective breeding, all of which act by enhancing the immune response. Currently, control planning is hampered by reliance on the faecal egg count (FEC), which suffers from low accuracy and a nonlinear and indirect relationship with infection intensity and host immune responses. We address this gap by using extensive parasitological, immunological and genetic data on the sheep-Teladorsagia circumcincta interaction to create an immunologically explicit model of infection dynamics in a sheep flock that links host genetic variation with variation in the two key immune responses to predict the observed parasitological measures. Using our model, we show that the immune responses are highly heritable and by comparing selective breeding based on low FECs versus high plasma IgA responses, we show that the immune markers are a much improved measure of host resistance. In summary, we have created a model of host-parasite infections that explicitly captures the development of the adaptive immune response and show that by integrating genetic, immunological and parasitological understanding we can identify new immune-based markers for diagnosis and control.
authors.affiliation: Institute of Biodiversity, Animal Health and Comparative Medicine, University of Glasgow, Garscube Campus, Bearsden Road, Glasgow G61 1QH, UK Boyd Orr Centre for Population and Ecosystem Health, University of Glasgow, Glasgow G61 1QH, UK joaquin.prada@glasgow.ac.uk.
authors.forename: Joaquín
authors.initials: J
authors.lastname: Prada Jiménez de Cisneros
authors.affiliation: Institute of Biodiversity, Animal Health and Comparative Medicine, University of Glasgow, Garscube Campus, Bearsden Road, Glasgow G61 1QH, UK Boyd Orr Centre for Population and Ecosystem Health, University of Glasgow, Glasgow G61 1QH, UK.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Stear
authors.affiliation: Institute of Biodiversity, Animal Health and Comparative Medicine, University of Glasgow, Garscube Campus, Bearsden Road, Glasgow G61 1QH, UK Boyd Orr Centre for Population and Ecosystem Health, University of Glasgow, Glasgow G61 1QH, UK.
authors.forename: Colette
authors.initials: C
authors.lastname: Mair
authors.affiliation: Institute of Biodiversity, Animal Health and Comparative Medicine, University of Glasgow, Garscube Campus, Bearsden Road, Glasgow G61 1QH, UK.
authors.forename: Darran
authors.initials: D
authors.lastname: Singleton
authors.affiliation: Institute of Biodiversity, Animal Health and Comparative Medicine, University of Glasgow, Garscube Campus, Bearsden Road, Glasgow G61 1QH, UK Boyd Orr Centre for Population and Ecosystem Health, University of Glasgow, Glasgow G61 1QH, UK.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Stefan
authors.affiliation: Institute of Biodiversity, Animal Health and Comparative Medicine, University of Glasgow, Garscube Campus, Bearsden Road, Glasgow G61 1QH, UK.
authors.forename: Abigail
authors.initials: A
authors.lastname: Stear
authors.affiliation: Biomathematics and Statistics Scotland, The King's Building, Edinburgh EH9 3JZ, UK.
authors.forename: Glenn
authors.initials: G
authors.lastname: Marion
authors.affiliation: Institute of Biodiversity, Animal Health and Comparative Medicine, University of Glasgow, Garscube Campus, Bearsden Road, Glasgow G61 1QH, UK Boyd Orr Centre for Population and Ecosystem Health, University of Glasgow, Glasgow G61 1QH, UK.
authors.forename: Louise
authors.initials: L
authors.lastname: Matthews
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D015415:Biomarkers; D001947:Breeding / Q000379:methods; D041981:Gastrointestinal Tract / Q000469:parasitology*; D014644:Genetic Variation; D006790:Host-Parasite Interactions; D055261:Immunogenetic Phenomena / Q000276:immunology*; D018448:Models, Immunological; D009349:Nematode Infections / Q000276:immunology / Q000662:veterinary*; D012756:Sheep / Q000235:genetics; D012757:Sheep Diseases / Q000276:immunology* / Q000469:parasitology*
chemical_list: D015415:Biomarkers
keywords: approximate Bayesian computation; helminth infections; host–parasite model; nematodes; selective breeding; sheep