Elucidating the Mechanisms Involved in the Regulation of Innate Antiviral Responses against Respiratory Pathogens in Chickens

阐明鸡呼吸道病原体先天抗病毒反应的调节机制

• 批准号: RGPIN-2021-03233
• 负责人: Barjesteh, Neda
• 金额: $ 2.19万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=742072
• 关键词: Elucidating; Mechanisms; Involved; Regulation; Innate

The poultry industry has a significant impact on the economy of Canada. However, the poultry industry is constantly at the risk of infectious diseases, including viral infections, which cause a high level of morbidity, even widespread mortality in poultry, and economic losses. There are several high priorities, economically important poultry viruses across Canada, including infectious bronchitis virus (IBV). Avian infectious bronchitis virus (IBV) is a highly contagious virus that causes mid-severe respiratory infections in chickens. Since 2017, several layer flocks have been slaughtered in Quebec and Ontario because of the false layer syndrome and significant decline in egg production. Flock depopulation and a severe decrease in egg production, secondary bacterial infections of the respiratory system following IBV infection cause significant economic losses to the poultry industry. One of the reasons for the unsuccessful attempts to control IBV infection is the gap in knowledge of host-virus interaction and viral pathogenesis at the molecular and cellular level. This research program addresses the interactions between the host and the virus. This program will focus on mechanisms that are crucial turning points in shaping antiviral immune responses and the outcome of viral infections. In fact, the effective elimination of viral infections depends on the coordinated communication between different cells of the immune system. Elucidating mechanisms involved in the cross-talk between different cells of the immune system is going to be a critical step to reach the ultimate goal of successfully enhance and tailor innate responses to shape adaptive immunity. To this end, the initial focus is on the dynamics of antiviral responses during IBV infection in the tracheal epithelial cells. Subsequently, the emphasis will be on the communication and cross-talk of tracheal epithelial cells with immune cells. We hypothesized that tracheal epithelial cells coordinate antiviral responses in the respiratory system during viral infection by influencing other cells of the immune system, which significantly affects the outcome of the infection. The proposed studies will provide fundamental and new insights into the immunological mechanisms of chicken tracheal epithelial cells in response to the infectious bronchitis virus. Furthermore, the discovery of underlying mechanisms involved in the initiation of antiviral responses and their impact on the adaptive immune responses provide the base information to improve current strategies and approaches to enhance mucosal and general immune responses.

家禽业对加拿大经济有重大影响。然而，家禽业经常面临包括病毒感染在内的传染病的风险，病毒感染导致家禽的高发病率，甚至广泛死亡，并造成经济损失。加拿大有几种高度优先的、经济上重要的家禽病毒，包括传染性支气管炎病毒（IBV）。禽传染性支气管炎病毒（IBV）是一种高度传染性病毒，可引起鸡的中重度呼吸道感染。自2017年以来，由于假蛋鸡综合征和产蛋量显著下降，魁北克和安大略省已经屠宰了几只蛋鸡。鸡群数量减少，产蛋量严重下降，IBV感染后继发的呼吸系统细菌感染给家禽业造成重大经济损失。控制IBV感染失败的原因之一是在分子和细胞水平上对宿主-病毒相互作用和病毒发病机制的认识存在差距。这个研究项目研究宿主和病毒之间的相互作用。该计划将侧重于形成抗病毒免疫反应和病毒感染结果的关键转折点的机制。事实上，病毒感染的有效消除依赖于免疫系统不同细胞之间的协调沟通。阐明免疫系统中不同细胞之间的串扰机制将是实现成功增强和调整先天反应以形成适应性免疫的最终目标的关键一步。为此，最初的重点是IBV感染期间气管上皮细胞的抗病毒反应动力学。随后，重点将放在气管上皮细胞与免疫细胞的通讯和串扰上。我们假设，在病毒感染期间，气管上皮细胞通过影响免疫系统的其他细胞来协调呼吸系统中的抗病毒反应，从而显著影响感染的结果。这些研究将为鸡气管上皮细胞对传染性支气管炎病毒的免疫机制提供基础和新的见解。此外，抗病毒反应启动的潜在机制及其对适应性免疫反应的影响的发现为改进当前增强粘膜和一般免疫反应的策略和方法提供了基础信息。