Genetic control of chicken heterophil function in advanced intercross lines: associations with novel and with known Salmonella resistance loci and a likely mechanism for cell death in extracellular trap production

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

Neutrophil extracellular traps and the dysfunctional innate immune response of cystic fibrosis lung disease:a review

Abstract Background Cystic Fibrosis (CF) is a devastating genetic disease characterised primarily by unrelenting lung inflammation and infection resulting in premature death and significant morbidity. Neutrophil Extracellular Traps (NETs) are possibly key to inflammation in the disease. This review aims to draw together existing research investigating NETs in the context of a dysfunctional innate immune system in CF. Main body NETs have a limited anti-microbial role in CF and studies have shown they are present in higher numbers in CF airways and their protein constituents correlate with lung function decline. Innate immune system cells express CFTR and myeloid-specific CFTR KO mice have greater neutrophil recruitment and higher pro-inflammatory cytokine production to both sterile and bacterial inflammatory challenges. CFTR KO neutrophils have impaired anti-microbial capacity and intrinsic abnormalities in the pH of their cytoplasm, abnormal protein trafficking, increased neutrophil elastase and myeloperoxidase function, and decreased hypochlorite concentrations in their phagolysosomes. Furthermore, neutrophils from CF patients have less intrinsic apoptosis and may be therefore more likely to make NETs. CFTR KO macrophages have high intraphagolysosomal pH and increased toll-like receptor 4 on their cell surface membranes, which inhibit their anti-microbial capacity and render them hyper-responsive to inflammatory stimuli, respectively. Pharmacological treatments for CF target these intrinsic abnormalities of immune dysfunction. Emerging evidence suggests that the absence of CFTR from neutrophils affects NETosis and the interaction of NETs with macrophages. Conclusion Current evidence suggests that NETs contribute to inflammation and lung destruction rather than working effectively in their anti-microbial capacity. Further studies focussing on the pro-inflammatory nature of NET constituents are required to identify the exact mechanistic role of NETs in CF and potential therapeutic interventions

Immune response gene expression in spleens of diverse chicken lines fed dietary immunomodulators

Vaccines, antibiotics, and other therapeutic agents used to combat disease in poultry generate recurring costs and the potential of residues in poultry products. Enhancing the immune response using alternative approaches such as selection for increased disease resistance or dietary immunomodulation may be effective additions to the portfolio of strategies the industry applies in poultry health management. The objective of this study was to characterize the effects of dietary supplementation with 3 immunomodulators [ascorbic acid, 1,3–1,6 β-glucans from baker\u27s yeast, and corticosterone] on cytokine gene expression in the spleen of 3 distinct genetic lines of chickens. Relative mRNA expression levels were determined using quantitative reverse transcriptase PCR for IL-1β, IL-2, inducible nitric oxide synthase, and toll-like receptors 4 and 15, all of which play important roles in chicken immune function. Expression data were analyzed by mixed model analysis. The only significant effect detected was sex effect (P \u3c 0.04) on expression of IL-1β. The present findings suggest the need for further investigations into the effects of dietary immunomodulators on cytokine gene expression in chickens so as to generate a better understanding of the immunomodulation process

Immune response gene expression in spleens of diverse chicken lines fed dietary immunomodulators

Vaccines, antibiotics, and other therapeutic agents used to combat disease in poultry generate recurring costs and the potential of residues in poultry products. Enhancing the immune response using alternative approaches such as selection for increased disease resistance or dietary immunomodulation may be effective additions to the portfolio of strategies the industry applies in poultry health management. The objective of this study was to characterize the effects of dietary supplementation with 3 immunomodulators [ascorbic acid, 1,3–1,6 β-glucans from baker's yeast, and corticosterone] on cytokine gene expression in the spleen of 3 distinct genetic lines of chickens. Relative mRNA expression levels were determined using quantitative reverse transcriptase PCR for IL-1β, IL-2, inducible nitric oxide synthase, and toll-like receptors 4 and 15, all of which play important roles in chicken immune function. Expression data were analyzed by mixed model analysis. The only significant effect detected was sex effect (P This article is published as Kumar, S., C. Ciraci, S. B. Redmond, P. Chuammitri, C. B. Andreasen, D. Palić, and S. J. Lamont. "Immune response gene expression in spleens of diverse chicken lines fed dietary immunomodulators." Poultry Science 90, no. 5 (2011): 1009-1013. DOI: 10.3382/ps.2010-01235. Posted with permission.</p

Immune response gene expression in spleens of diverse chicken lines fed dietary immunomodulators

Vaccines, antibiotics, and other therapeutic agents used to combat disease in poultry generate recurring costs and the potential of residues in poultry products. Enhancing the immune response using alternative approaches such as selection for increased disease resistance or dietary immunomodulation may be effective additions to the portfolio of strategies the industry applies in poultry health management. The objective of this study was to characterize the effects of dietary supplementation with 3 immunomodulators [ascorbic acid, 1,3–1,6 β-glucans from baker\u27s yeast, and corticosterone] on cytokine gene expression in the spleen of 3 distinct genetic lines of chickens. Relative mRNA expression levels were determined using quantitative reverse transcriptase PCR for IL-1β, IL-2, inducible nitric oxide synthase, and toll-like receptors 4 and 15, all of which play important roles in chicken immune function. Expression data were analyzed by mixed model analysis. The only significant effect detected was sex effect (P \u3c 0.04) on expression of IL-1β. The present findings suggest the need for further investigations into the effects of dietary immunomodulators on cytokine gene expression in chickens so as to generate a better understanding of the immunomodulation process