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A previous study demonstrated that inbred line 0 chickens are more resistant to low-pathogenicity avian influenza (LPAI) infection than line CB.12 birds based on viral shedding, but the resistance was not associated with higher AIV-specific IFN\u03b3 responses or antibody titres. In this study, we investigated the proportions and cytotoxic capacity of T-cell subpopulations in the spleen and the early immune responses in the respiratory tract, analysing the innate immune transcriptome of lung-derived macrophages following in vitro stimulation with LPAI H7N1 or the TLR7 agonist R848. The more susceptible C.B12 line had a higher proportion of CD8\u03b1\u03b2+ \u03b3\u03b4 and CD4+CD8\u03b1\u03b1+ \u03b1V\u03b21 T cells, and a significantly higher proportion of the CD8\u03b1\u03b2+ \u03b3\u03b4 and CD8\u03b1\u03b2+ \u03b1V\u03b21 T cells expressed CD107a, a surrogate marker of degranulation. Lung macrophages isolated from line C.B12 birds expressed higher levels of the negative regulator genes TRIM29 and IL17REL, whereas macrophages from line 0 birds expressed higher levels of antiviral genes including IRF10 and IRG1. After stimulation with R848, the macrophages from line 0 birds mounted a higher response compared to line C.B12 cells. Together, the higher proportion of unconventional T cells, the higher level of cytotoxic cell degranulation ex vivo and post-stimulation and the lower levels of antiviral gene expression suggest a potential role of immunopathology in mediating susceptibility in C.B12 birds.<\/jats:p>","DOI":"10.3390\/v15030591","type":"journal-article","created":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T03:59:16Z","timestamp":1677038356000},"page":"591","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Comparative Analysis of Different Inbred Chicken Lines Highlights How a Hereditary Inflammatory State Affects Susceptibility to Avian Influenza Virus"],"prefix":"10.3390","volume":"15","author":[{"given":"Karen J.","family":"Bryson","sequence":"first","affiliation":[{"name":"Division of Immunology, The Roslin Institute & R(D)SVS, University of Edinburgh, Easter Bush, Edinburgh EH25 9RG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Sives","sequence":"additional","affiliation":[{"name":"Division of Immunology, The Roslin Institute & R(D)SVS, University of Edinburgh, Easter Bush, Edinburgh EH25 9RG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui-Min","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Virology, The Roslin Institute & R(D)SVS, University of Edinburgh, Easter Bush, Edinburgh EH25 9RG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominika","family":"Borowska","sequence":"additional","affiliation":[{"name":"Division of Immunology, The Roslin Institute & R(D)SVS, University of Edinburgh, Easter Bush, Edinburgh EH25 9RG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2813-7872","authenticated-orcid":false,"given":"Jacqueline","family":"Smith","sequence":"additional","affiliation":[{"name":"Division of Genome Biology, The Roslin Institute & R(D)SVS, University of Edinburgh, Easter Bush, Edinburgh EH25 9RG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0872-9440","authenticated-orcid":false,"given":"Paul","family":"Digard","sequence":"additional","affiliation":[{"name":"Division of Virology, The Roslin Institute & R(D)SVS, University of Edinburgh, Easter Bush, Edinburgh EH25 9RG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2241-1743","authenticated-orcid":false,"given":"Lonneke","family":"Vervelde","sequence":"additional","affiliation":[{"name":"Division of Immunology, The Roslin Institute & R(D)SVS, University of Edinburgh, Easter Bush, Edinburgh EH25 9RG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"20180257","DOI":"10.1098\/rstb.2018.0257","article-title":"A brief history of bird flu","volume":"374","author":"Lycett","year":"2019","journal-title":"Philos. 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