Genetic and dietary effects on chicken heterophil function and immune response to Salmonella enteritidis

The function of the chicken innate immune system against pathogens is affected by genetic background and immune modulating diet. Heterophils from broiler, Leghorn, and Fayoumi birds showed differential expression of immune genes when stimulated with Salmonella enteritidis (SE) bacteria, a zoonotic pathogen. Heterophils from Fayoumi chickens increased expression of both pro-inflammatory and anti-inflammatory cytokines following stimulation, while the broiler and Leghorn lines did not show any significant elevation of these transcripts. Similarly, birds from the broiler line did not show any change in splenic gene expression following diet treatments with immunomodulators: beta-glucans, ascorbic acid, or corticosterone. The Leghorn and Fayoumi lines altered splenic expression of interleukin-4 (IL-4), IL-6, and IL-18 in response to immune modulating diet. Gene expression of SE stimulated heterophils from Leghorn and Fayoumi birds was lower for the corticosterone treatment group but did not change significantly compared to controls in the beta-glucan or ascorbic acid treatment groups. The proportion of circulating heterophils was significantly increased for Leghorns fed the corticosterone diet but not in birds from the Fayoumi line. A genome-wide scan of single nucleotide polymorphism (SNP) markers in broiler X Leghorn and broiler X Fayoumi advanced intercross lines revealed significant association of heterophil function with known SE resistance loci and previously uncharacterized genes. Production of heterophil extracellular traps (HETs) was linked to the previously identified SAL1 locus and supported the proapoptotic regulator Siva-1 as a candidate gene affecting this phenotype. Both HET production and phagocytosis of SE bacteria were linked to SLC11A1, which contains polymorphisms associated with resistance to intracellular bacteria. A region on chromosome 3 was associated with changes in heterophil phagocytosis influenced by both SNP genotype and diet effects, with peak associations at the SLC4A1AP and BTBD9 gene loci, and a predicted gene locus on chromosome 6 was associated with HET production. The identification of differences in immune response between genetic lines and genomic locations which regulate these differences is important for making selection decisions to improve disease resistance in chickens.