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      Innate immune response to double-stranded RNA in American heritage chicken breeds

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          Abstract

          Backyard poultry flocks that employ heritage breeds of chicken play a crucial role in the maintenance of poultry pathogens of economic and zoonotic importance. This study examined innate immunity to viral pathogens in heritage chicken breeds using a model of viral double-stranded RNA ( dsRNA). Following intraperitoneal injection of high molecular weight ( HMW) -poly(I:C)/Lyovec into 4-wk-old chicks, we evaluated gene expression in peripheral blood mononuclear cells ( PBMCs) and splenocytes. There was a significant difference across breeds in the expression of IL-4, IL-12p40, IFNγ, and B-cell activating factor ( BAFF) in the spleen. In PBMCs, a significant difference in IFN-α expression was seen across breeds. Approximately 57% of IFN-α transcripts in PBMCs was explained by levels of expression of MDA5 transcripts. Using flow cytometry, we showed that only monocytes/macrophages (KUL01+ cells) expressed the scavenger receptor CD163. Regression analysis showed that 42% of fold change in CD163 expression on PBMCs was explained by breed ( P < 0.0004). In general, breeds that responded to HMW-poly(I:C) by showing higher upregulation of IFNγ, IL-1β, and IL-12p40 transcripts in the spleen, and higher IFNα transcripts in peripheral blood, expressed less CD163 on blood monocytes. These findings suggest a genetic basis for the response of chickens to double-stranded RNA. Surface expression of the scavenger receptor CD163 in PBMCs following injection of high molecular weight poly(I:C) may be a rapid method to select chickens for breeding based on innate immune response to viral dsRNA.

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          The history of Toll-like receptors - redefining innate immunity.

          The discovery of Toll-like receptors (TLRs) was an important event for immunology research and was recognized as such with the awarding of the 2011 Nobel Prize in Physiology or Medicine to Jules Hoffmann and Bruce Beutler, who, together with Ralph Steinman, the third winner of the 2011 Nobel Prize and the person who discovered the dendritic cell, were pioneers in the field of innate immunity. TLRs have a central role in immunity - in this Timeline article, we describe the landmark findings that gave rise to this important field of research.
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            Length-dependent recognition of double-stranded ribonucleic acids by retinoic acid–inducible gene-I and melanoma differentiation–associated gene 5

            The ribonucleic acid (RNA) helicases retinoic acid-inducible gene-I (RIG-I) and melanoma differentiation–associated gene 5 (MDA5) recognize distinct viral and synthetic RNAs, leading to the production of interferons. Although 5′-triphosphate single-stranded RNA is a RIG-I ligand, the role of RIG-I and MDA5 in double-stranded (ds) RNA recognition remains to be characterized. In this study, we show that the length of dsRNA is important for differential recognition by RIG-I and MDA5. The MDA5 ligand, polyinosinic-polycytidylic acid, was converted to a RIG-I ligand after shortening of the dsRNA length. In addition, viral dsRNAs differentially activated RIG-I and MDA5, depending on their length. Vesicular stomatitis virus infection generated dsRNA, which is responsible for RIG-I–mediated recognition. Collectively, RIG-I detects dsRNAs without a 5′-triphosphate end, and RIG-I and MDA5 selectively recognize short and long dsRNAs, respectively.
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              Gain-of-function mutations in IFIH1 cause a spectrum of human disease phenotypes associated with upregulated type I interferon signaling

              The type I interferon system is integral to human antiviral immunity. However, inappropriate stimulation or defective negative regulation of this system can lead to inflammatory disease. We sought to determine the molecular basis of genetically uncharacterized cases of the type I interferonopathy Aicardi-Goutières syndrome, and of other patients with undefined neurological and immunological phenotypes also demonstrating an upregulated type I interferon response. We found that heterozygous mutations in the cytosolic double-stranded RNA receptor gene IFIH1 (MDA5) cause a spectrum of neuro-immunological features consistently associated with an enhanced interferon state. Cellular and biochemical assays indicate that these mutations confer a gain-of-function - so that mutant IFIH1 binds RNA more avidly, leading to increased baseline and ligand-induced interferon signaling. Our results demonstrate that aberrant sensing of nucleic acids can cause immune upregulation.
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                Author and article information

                Contributors
                Journal
                Poult Sci
                Poult Sci
                Poultry Science
                Elsevier
                0032-5791
                1525-3171
                23 November 2023
                February 2024
                23 November 2023
                : 103
                : 2
                : 103318
                Affiliations
                [* ]Department of Pathobiology, College of Veterinary Medicine, Tuskegee University, Tuskegee, AL 36088
                []Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211, USA
                []Department of Animal Husbandry and Animal Wealth Development, Faculty of Veterinary Medicine, Alexandria University, Alexandria, Egypt
                Author notes
                [1 ]Corresponding author: odemuyiwas@ 123456missouri.edu
                Article
                S0032-5791(23)00837-4 103318
                10.1016/j.psj.2023.103318
                10757028
                38064884
                6fb51857-9721-4be9-8224-bcfeba2d40de

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 25 July 2023
                : 20 November 2023
                Categories
                IMMUNOLOGY, HEALTH AND DISEASE

                dsrna,cytokine transcript,cd163,american heritage chicken

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