Role of avian macrophages in the pathogenesis of infectious bronchitis virus infection

家禽肉和鸡蛋是加拿大饮食中蛋白质的重要来源。加拿大家禽业的价值约为39亿美元（2014年），占加拿大农业经营现金收入的6.9%，年产量为6.63亿只家禽和70亿枚鸡蛋。然而，家禽业的主要限制是与通过呼吸道粘膜进入的病毒相关的发病率和死亡率。例如，传染性支气管炎（IB）是一种高度传染性的呼吸道病毒感染，对健康、生产力和成本具有全球性影响（包括对北美鸡的重大影响）。IB的控制主要集中在含有实验室减毒病毒的疫苗上，但在接种疫苗的鸡中经常发生IB爆发。原因有二。首先，弱疫苗病毒在通过鸡群后变为致病性。其次，野外IB病毒（IBV）（抵抗疫苗接种施加的压力）突变为更具毒性的形式会导致严重的疾病。因此，迫切需要一种新的方法来减轻这种疾病的影响。宿主和IBV之间的相互作用，以及导致病毒清除或鸡疾病进展的机制，知之甚少。作为第一步，需要关于宿主-病毒相互作用的复杂性的新知识，特别是针对IBV引起的宿主反应。为了阐明宿主-病毒相互作用，最初的重点将放在巨噬细胞上，巨噬细胞是已知在哺乳动物中对病毒感染的非特异性和特异性宿主反应中起主要作用的细胞。然而，禽巨噬细胞是否在鸡IB的疾病进展中起作用，以及鸡中针对IBV感染的非特异性和特异性宿主应答，尚未得到很好的表征。因此，将研究巨噬细胞以及巨噬细胞产生的介质（如一氧化氮和白细胞介素）在引起鸡IB和/或赋予鸡IB抗性中的作用。*拟议的研究将产生关于宿主和IBV之间相互作用的新知识，以及导致病毒清除或鸡疾病发展的机制。鉴于目前在这一领域的知识缺乏，拟议的研究预计将提供新的见解巨噬细胞在宿主反应和疾病进展的鸡IBV感染的作用。拟议研究的长期目标是为控制IBV感染的免疫干预策略提供基础，IBV感染在加拿大流行，并在全球范围内造成家禽业的重大经济损失。

Poultry meat and eggs are important sources of protein in the Canadian diet. Canada's poultry industry has been valued at ~ $3.9 billion (2014), contributing 6.9% of cash receipts to farming operations in Canada with annual production of 663 million birds and >7 billion eggs. However, a major limitation of the poultry industry is morbidity and mortality associated with viruses that enter via the respiratory mucosa. For example, infectious bronchitis (IB) is a highly contagious respiratory viral infection, with global impacts (including substantial effects on North American chickens) on health, productivity and costs. Control of IB is focused on vaccines containing laboratory-attenuated viruses, but there are frequently IB outbreaks in vaccinated chickens. There are two reasons for this. Firstly, weakened vaccine virus becomes pathogenic after passage through the flock. Secondly, mutation of field IB virus (IBV) (against the pressure imposed by vaccination) to more virulent forms causes severe disease. Consequently, a novel approach to mitigate effects of this disease is urgently required. Interactions between the host and IBV, as well as mechanisms that lead to either virus clearance or disease progression in chickens, are poorly understood. As a first step, new knowledge regarding the complexity of host-virus interactions, particularly host responses elicited against IBV, is required.****To elucidate host-virus interactions, the initial focus will be on macrophages, cells known to have major roles in non-specific and specific host responses against viral infections in mammals. However, whether avian macrophages have roles in the disease progression of IB in chickens, as well as non-specific and specific host responses against IBV infection in chickens, has not been well characterized. Therefore, the roles of macrophages as well as the mediators produced by macrophages such as nitric oxide and interleukins in causing IB and/or conferring resistance against IB in chickens, will be studied.****The proposed studies will produce new knowledge regarding interactions between the host and IBV, and mechanisms that lead to virus clearance or disease development in chickens. Given the paucity of current knowledge in this area, the proposed studies are expected to provide novel insights into the role of macrophages in host responses and disease progression of IBV infection in chickens. The long-term goal of the proposed research is to provide a basis for immune intervention strategies for the control of IBV infection, which is prevalent in Canada and globally causing significant economic losses in poultry industry.****