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.

External disturbances impact helminth–host interactions by affecting dynamics of infection, parasite traits, and host immune responses

“…For instance, sheep IgA was found to regulate Teladorsagia circumcincta growth and eggs in utero (Henderson & Stear, ; Stear et al, ). IgA was also suggested to be a good indicator of heritable host resistance to helminths (Prada Jiménez de Cisneros et al, ; Strain et al, ). We previously showed that IgA is important for the control of T. retortaeformis intensity of infection (Takar et al, ).…”

“…For instance, sheep IgA was found to regulate Teladorsagia circumcincta growth and eggs in utero (Henderson & Stear, 2006;Stear et al, 2004). IgA was also suggested to be a good indicator of heritable host resistance to helminths (Prada Jiménez de Cisneros et al, 2014;Strain et al, 2002).…”

The control of sea lice in Atlantic salmon by selective breeding

“…Based on our model, which has been fitted to field data from Scottish salmon farms [ 34 ] and parametrized using field trials to assess genetic variation in susceptibility, breeding for resistance to sea lice would reduce levels of infective larvae by reducing the number of individuals with high numbers of lice. This environmental benefit is not captured in traditional methods of estimating the response to selective breeding and was achieved by integrating quantitative genetics into an epidemiological model [ 47 – 49 ], allowing genetic variation between individuals and selective breeding to be modelled.…”

A simulation model to investigate interactions between first season grazing calves and Ostertagia ostertagi

“…As with parasite establishment, the fecundity (eggs/female) was assumed to decline towards a plateau as immunity was acquired ( Michel, 1969 ). The immune response effect on fecundity was assumed to develop at a different rate to the establishment and mortality due to different underlying immune mechanisms ( Stear et al, 1995 , Prada Jiménez de Cisneros et al, 2014 ). As with EM the eggs per female was plotted against larvaldays from the experiment A of Michel (1969) ; the data suggest an exponential relationship between larvaldays and fecundity ( F ), taking the form: where F max is the maximum number of eggs per female worm, F min is the minimum number of eggs per female worm and k F is the constant of the relationship between larvaldays and fecundity.…”