Comparative Analysis of Different Inbred Chicken Lines Highlights How a Hereditary Inflammatory State Affects Susceptibility to Avian Influenza Virus

• Published in: Viruses Vol. 15; no. 3; p. 591
• Main Authors: Bryson, Karen J, Sives, Samantha, Lee, Hui-Min, Borowska, Dominika, Smith, Jacqueline, Digard, Paul, Vervelde, Lonneke
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 21-02-2023; MDPI
• Subjects: Animals; Antibodies; Antiviral Agents; Avian flu; avian influenza virus; Avian influenza viruses; Birds; CD4 antigen; chicken; Chicken breeds; Chickens; Comparative analysis; Cytotoxicity; Degranulation; Flow cytometry; Gene expression; Genes; Genetic aspects; genetic variation; Haplotypes; Health aspects; Heat; immune response; Inbreeding; Infections; Inflammation; Influenza; Influenza A; Influenza A virus; Influenza A Virus, H7N1 Subtype; Influenza in Birds; Lymphocytes T; Macrophages; Pandemics; Pathogenicity; Poultry; Respiratory tract; Spleen; TLR7 protein; Toll-like receptors; Transcriptomes; Viruses; Zoonoses; γ-Interferon; United Kingdom; United Kingdom > UK; United States > US; Germany; genetic variation; chicken; immune response; inflammation; avian influenza virus
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v15030591

Evidence suggests that susceptibility to avian influenza A virus in chickens is influenced by host genetics, but the mechanisms are poorly understood. 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 IFNγ 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 CD8αβ
γδ and CD4
CD8αα
αVβ
T cells, and a significantly higher proportion of the CD8αβ
γδ and CD8αβ
αVβ
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
and
whereas macrophages from line 0 birds expressed higher levels of antiviral genes including
and
. 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.