Genetic control of chicken heterophil function in advanced intercross lines: associations with novel and with known <Emphasis Type="Italic">Salmonella</Emphasis> resistance loci and a likely mechanism for cell death in extracellular trap production |
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Authors: | Sarah B Redmond Phongsakorn Chuammitri Claire B Andreasen Dušan Palić Susan J Lamont |
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Institution: | (1) Department of Animal Science, Iowa State University, Ames, IA 50011, USA;(2) Department of Veterinary Microbiology and Preventative Medicine, Iowa State University, Ames, IA 50011, USA;(3) Department of Veterinary Pathology, Iowa State University, Ames, IA 50011, USA;(4) Department of Biomedical Sciences, Iowa State University, Ames, IA 50011, USA; |
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Abstract: | Heterophils, the avian polymorphonuclear leukocyte and the counterpart of mammalian neutrophils, generate the primary innate
response to pathogens in chickens. Heterophil performance against pathogens is associated with host disease resistance, and
heterophil gene expression and function are under genetic control. To characterize the genomic basis of heterophil function,
heterophils from F13 advanced intercross chicken lines (broiler × Leghorn and broiler × Fayoumi) were assayed for phagocytosis and killing of
Salmonella enteritidis, oxidative burst, and extracellular trap production. A whole-genome association analysis of single nucleotide polymorphisms
at 57,636 loci identified genomic locations controlling these functional phenotypes. Genomic analysis revealed a significant
association of extracellular trap production with the SAL1 locus and the SLC11A1 gene, which have both been previously associated with resistance to S. enteritidis. Fine mapping supports SIVA1 as a candidate gene controlling SAL1-mediated resistance and indicates that the proposed cell-death mechanism associated with extracellular trap production, ETosis,
likely functions through the CD27/Siva-1-mediated apoptotic pathway. The SLC11A1 gene was also associated with phagocytosis of S. enteritidis, suggesting that the Slc11a1 protein may play an additional role in immune response beyond depleting metal ions to inhibit
intracellular bacterial growth. A region of chromosome 6 with no characterized genes was also associated with extracellular
trap production. Further characterization of these novel genes in chickens and other species is needed to understand their
role in polymorphonuclear leukocyte function and host resistance to disease. |
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