In the near future, a broader definition of breeding goals should balance productivity with improved functional traits such as health, in order to describe animals as an integrated component of sustainable production systems. In this context, there is a need to study the genetic control of general immune response and analyse whether health traits referred to as immunocompetence might be included in future selection schemes. In collaboration with pig breeders, we have started a large survey of innate and adaptive immune response in French Large White pigs (IMMOPIG project, ANR 2007-2009) and moderate to strong heritability estimates have been obtained for the majority of the traits investigated, showing that immune response is largely under genetic control, in agreement with reports from other laboratories. Animals of the IMMOPIG project are being genotyped with porcine 60K iSelect chips for genetic association studies. In addition, a divergent selection for an index of four immune parameters has been launched and animals of the G1 generation will be born in 2010. Commensal bacteria inhabit all body surfaces that are exposed to environment and the lower gastrointestinal tract may be considered as the best example of bacteria hostage with a possible coevolution of host and bacteria. The gut microbiota develops as a host-specific parameter that gets stabilized early during lifetime. There is a growing interest in studying the relationships between the mammalian immune system and the bacteria that are present in the mammalian gut. Analyzing microbiota as a potent relevant phenotype to integrate into a global approach on immunocompetence represents a prospective and original approach. The aim of the work will be to study gut microbiota in pigs that are scored for conventional immune response and consider the gut microbiota as a new parameter to include in genetic analysis. The project is divided into two main parts. On the one hand, global studies including microbiota characterisation, animal phenotyping and genotyping will be carried out. On the other hand, local studies targeting interactions between gut epithelium and microbiota will be investigated for a subgroup of piglets well characterized for phenotypes and genotypes. Ninety mononuclear families will be produced and four piglets per family will be studied. Microbiota of 60 day-old piglets will be characterized together with the microbiota of the sows after piglet birth. Variation of microbiota during early lifetime will be studied for a subset of 30 piglets from birth to the growing period. Microbiota heritability and correlations between gut microbiota and immune response parameters will be calculated. The 360 piglets and the 90 boars will be genotyped using the genome-wide porcine 60K iSelect chips in order to accumulate preliminary data for further genome-wide association studies. Major Histocompatibility Complex haplotypes and Toll-like receptor polymorphisms will be characterised. Local interaction studies will be carried out on the subgroup of 30 piglets followed for microbiota variations. We shall have the possibility to also include animals produced during the ongoing divergent selection on an immunity index. The differential expression of the host genes at five distinct gut sites (duodenum, jejunum, ileum, colon and Peyer’s patches) will be studied by a transcriptomic approach. We will target three key functions of local immunity: histocompatibility by analysing expression of non-classical class I genes (SLA-Ib, MIC-2, MR1, CD1), motif recognition at the cell surface (TLRs, NODs) and analysis of IgA immune response expansion. In addition, peripheric T lymphocytes will be compared to intestinal T lymphocytes.
