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

家禽业对加拿大的经济有重大影响。然而，家禽养殖业经常面临传染病的风险，包括病毒感染，这导致高水平的发病率，甚至家禽的广泛死亡和经济损失。加拿大各地有几种高度优先、具有重要经济意义的禽类病毒，包括传染性支气管炎病毒(IBV)。禽传染性支气管炎病毒(IBV)是一种引起鸡中重度呼吸道感染的高度传染性病毒。自2017年以来，魁北克和安大略省已有几只蛋鸡因假蛋鸡综合症和鸡蛋产量大幅下降而被宰杀。鸡群数量减少和产蛋量的严重下降，以及IBV感染后呼吸系统的继发性细菌感染，给养禽业造成了重大的经济损失。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致病机制的了解不足。这项研究计划解决宿主和病毒之间的相互作用。该计划将重点研究在形成抗病毒免疫反应和病毒感染结果方面具有关键转折点的机制。事实上，有效消除病毒感染有赖于免疫系统不同细胞之间的协调沟通。阐明免疫系统不同细胞之间相互作用的机制将是实现成功增强和定制先天反应以形成适应性免疫的最终目标的关键一步。为此，最初的重点是在IBV感染气管上皮细胞期间的抗病毒反应的动态。随后，重点将放在气管上皮细胞与免疫细胞之间的交流和相互作用上。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的抗病毒反应，从而显著影响感染的结果。拟议的研究将为鸡的气管上皮细胞对传染性支气管炎病毒的免疫应答机制提供基本的和新的见解。此外，抗病毒应答的启动及其对获得性免疫应答的影响的潜在机制的发现为改进现有的增强粘膜和全身免疫应答的策略和方法提供了基础信息。

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.