Morphologic characterization and cytokine response of chicken bone-marrow derived dendritic cells to infection with high and low pathogenic avian influenza virus

Authors: MO, JONG SUK - Orise Fellow; SEGOVIA, KAREN - Csl Seqirus; CHRZASTEK, KLAUDIA - Animal And Plant Health Agency; BRIGGS, KELSEY - Orise Fellow; Kapczynski, Darrell

Submitted to: Frontiers in Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/23/2024
Publication Date: N/A
Citation: N/A

Interpretive Summary: Avian influenza is a disease caused by infection with avian influenza virus (AIV) which can result in significant morbidity and mortality in both domestic poultry and wild birds. The immune response of birds to AIV is still largely unknown, especially the contributions of immune cell populations. A better understanding of how the virus evades the immune system can aid in the discovery of disease resistance pathways. In these studies, we produced a special type of immune cell, dendritic cells (DCs), that function as antigen presenting cells for the immune system. The purpose was to determine how the cells and the virus interact. Results demonstrate that AIV is able to replicate inside of DCs and cause enhanced cytokine expression that ultimately resulted in cell death. This research offers opportunity to study how the virus can defeat the immune response which can then be applied for counter measure approaches.

Technical Abstract: Dendritic cells (DCs) are professional antigen-presenting cells, which are key components of the immune system and involved in the early immune response. DCs are specialized in capturing, processing, and presenting antigens to facilitate immune interactions. Chickens infected with avian influenza virus (AIV) demonstrate a wide range of clinical symptoms, based on pathogenicity of the virus. Low pathogenic avian influenza (LPAI) viruses typically induce mild clinical signs, whereas high pathogenic avian influenza (HPAI) induce more severe disease, which can lead to death within days. For this study, chicken bone marrow-derived DC (ckBM-DC)s were produced and infected with high and low pathogenic avian influenza viruses of H5N2 or H7N3 subtypes to characterize innate immune responses, study effect on cell morphology, and evaluate virus replication. A strong proinflammatory response, including chicken interleukin-1ß, and stimulation of the interferon response pathway were observed at 8 hours post infection. Microscopically, the DCs underwent morphological changes from classic elongated dendrites to a more general rounded shape that eventually lead to cell death with the presence of scattered cellular debris. Differences in onset of morphologic changes were observed between H5 and H7 subtypes. Increases in viral titers demonstrated that both HPAI and LPAI are capable of infecting and replicating in DCs. The elevated expression of infected DCs may be indicative with a dysregulation of the immune response typically seen with HPAI infections.