Innate immunity to swine influenza virus in its natural host

猪流感病毒(SIV)是猪流感的病原，是一种高度传染性的猪急性病毒性疾病。SIV导致急性呼吸道感染和肺部损害，由于身体状况下降和达到市场体重所需天数的增加而造成经济损失。 先天免疫是宿主对抗包括病毒病原体在内的微生物病原体的第一道防线。核苷酸结合结构域富含亮氨酸重复序列的分子(NLR)是识别病原体相关分子模式的三种传感器之一。关于NLRs在感知流感病毒在其自然宿主中的感染方面的作用，人们知之甚少。在本方案中，我们将利用SIV的自然宿主猪来研究NLR和炎症小体在控制SIV感染中的作用。这项建议的长期目标是剖析猪感染流感病毒时宿主的先天免疫反应。具体地说，我们将研究NLRP3炎症体在调节流感病毒感染反应中的功能。我们推测，在SIV感染过程中，炎症体信号通路被激活，它在保护猪免受SIV感染中起着重要作用。我们将通过以下具体目标来检验我们的假设：1)。猪SIV感染后炎性细胞因子表达及肺病理变化特征。2)。猪上皮细胞、巨噬细胞和树突状细胞中炎性小体途径激活的特征。3)。流感病毒感染后炎症小体被激活的机制研究。了解自然宿主对SIV感染的先天免疫反应，特别是针对NLRP3炎症体途径增强功能，可能成为对抗流感病毒感染的新的治疗工具。

Swine influenza virus (SIV) is the causative pathogen for swine influenza, a highly contagious, acute viral disease of swine. SIV induces an acute respiratory tract infection and lung lesions, causing economic losses due to decreased body condition and an increase in the number of days needed to reach market weight. The innate immunity is the first line of the host to fight against microbial pathogens, including viral pathogens. The nucleotide-binding domain-leucine-rich repeat-containing molecule (NLR) is one of the three sensors that recognize pathogen-associated molecular patterns presented within the pathogens. Little is known about the role of NLRs in sensing influenza virus infection in its natural host. In this proposal, we will utilize pigs, the natural host of SIV, to study the role of NLR and inflammasome in controlling SIV infection. The long term objective of this proposal is to dissect the host innate immune responses upon influenza virus infection in pigs. Specifically, we will study the function of the NLRP3 inflammasome in mediating response to influenza virus infection. We hypothesize that inflammasome signaling pathway is activated during SIV infection and it plays an important role in protection against SIV infection in pigs. We will test our hypothesis with the following specific aims: 1). Characterization of inflammatory cytokine expression and lung pathology in pigs after SIV infection. 2). Characterization of inflammasome pathway activation in porcine epithelial cells, macrophages and dendritic cells. 3). Investigation of the mechanism by which inflammasome is activated in response to influenza virus infection. Understanding the innate immune responses to SIV infection in its natural host, specifically targeting the NLRP3 inflammasome pathway for enhanced function may become a novel therapeutic tool to combat influenza virus infection.