The Impact of Bacterial Co-Infectin on Respiratory Virus-Specific T cell Response

细菌共感染对呼吸道病毒特异性 T 细胞反应的影响

• 批准号: 8089283
• 负责人: Hao Shen
• 金额: $ 33.43万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8089283
• 关键词: Address; Adult; Affect; Bacteria; Bacterial Infections; Bacterial Pneumonia; Bronchi; Bystander Effect; Cells; Cessation of life; Child; Complex; Complication; Disease; Disease Outbreaks; Disease Outcome; Epithelium; Equilibrium; Foundations; Generations; Goals; Gram-Positive Bacteria; Hand; Hemophilus; Hong Kong; Host resistance; Human; Human Influenza A Virus; Immune response; Immunity; Immunologic Memory; Impairment; Infant; Infection; Infiltration; Inflammation; Inflammation Mediators; Inflammatory; Inflammatory Response; Influenza; Influenza A virus; Interferons; Interleukin-12; Intervention; Lower Respiratory Tract Infection; Lower respiratory tract structure; Lung; Mediating; Mediator of activation protein; Memory; Modeling; Mus; Nasopharynx; Nose; Pathology; Pattern; Phase; Play; Pneumonia; Population; Predisposition; Production; Relative (related person); Respiratory Mucosa; Respiratory System; Respiratory physiology; Respiratory tract structure; Role; Route; Severity of illness; Signal Transduction; Staphylococcus aureus; Streptococcus pneumoniae; T cell response; T memory cell; T-Cell Activation; T-Lymphocyte; Testing; Time; Trachea; United States; Upper respiratory tract; Viral; Viral Pneumonia; Virus Diseases; Virus Replication; anti-influenza; chemokine; cytokine; experience; immunopathology; in vivo; influenza epidemic; influenzavirus; mortality; novel strategies; pandemic disease; pandemic influenza; pathogen; prevent; respiratory virus; response; seasonal influenza; superinfection; virus pathogenesis

Influenzae A virus (IAV) is highly contagious and is responsible for outbreaks of seasonal flu. In humans, IAV infection is usually confined to the epithelia of nasopharynx, trachea and large bronchi. Only in some cases does the infection progress to a primary viral pneumonia. However, secondary bacterial pneumonia is a frequent and serious complication with high mortality. In addition to annual influenza epidemics, there is an ever-present threat of a global pandemic and several recent pandemics have inflicted widespread devastation. In the majority of cases, the high mortality associated with these influenza pandemics is not due to primary viral pneumonia, but is instead caused by secondary bacterial infections. Streptococcus pneumoniae (Sp) is a Gram-positive bacterium that is the leading cause of secondary bacterial pneumonia associated with both influenza epidemics and pandemics. The effect of IAV infection on host susceptibility to Sp has been studied extensively in the murine model. However, limited information is available on how Sp may affect the course of IAV infection, and consequently, disease outcome. Even less is known about how Sp co-infection may affect the generation of immunological memory and anti-flu immunity. Our recent results have shown that inflammation induced by a bacterial pathogen can have opposing effects on different phases of the adaptive immune response. These results have important implications that are particularly relevant to co-infection where inflammatory responses induced by one pathogen can have bystander effects on the other pathogen. As such, we hypothesize that inflammation induced by Sp could alter host resistance/susceptibility to IAV and influence the lAV-specific adaptive immune response. We will test our hypothesis by 1) determining the effect of Sp co-infection on host resistance/susceptibility to IAV infection, 2) studying the role of inflammatory responses in mediating protection or immunopathology during lAV/Sp coinfection, 3) determine the effect of Sp co-infection on CDS T cell responses to IAV and lAV-specific CDS T cell memory. At the end of this study, we hope to gain a better understanding of the complex host-virusbacterium interactions occuring during co-infection, with the goal of developing interventions that will shift the balance of the interaction to benefit the host.

甲型流感病毒(IAV)具有高度传染性，是季节性流感爆发的罪魁祸首。在人类身上，IAV 感染通常局限于鼻咽、气管和大支气管的上皮细胞。仅在某些情况下 感染是否会进展为原发病毒性肺炎。然而，继发性细菌性肺炎是一种 并发症多、重，死亡率高。除了每年的流感流行之外，还有一种 全球大流行的无处不在的威胁和最近的几次大流行造成了广泛的 毁灭。在大多数情况下，与这些流感大流行相关的高死亡率并不是 原发病毒性肺炎，而不是由继发性细菌感染引起。链球菌 肺炎(Sp)是一种革兰氏阳性细菌，是继发性细菌性肺炎的主要原因 与流感流行和大流行有关。鸡传染性胃炎病毒感染对宿主易感性的影响 在小鼠模型中，SP已被广泛研究。然而，关于Sp如何实现的信息有限 可能会影响IAV感染的进程，从而影响疾病的结局。更不知道它是如何 SP合并感染可能影响免疫记忆和抗流感免疫的产生。我们最近的结果 已经表明由细菌病原体引起的炎症可以对不同的 适应性免疫反应的各个阶段。这些结果具有重要的影响，尤其是 与由一种病原体引起的炎症反应可产生旁观者效应的混合感染有关 在另一种病原体上。因此，我们假设Sp引起的炎症可以改变宿主 对IAV的抗性/敏感性，并影响LAV特异性的获得性免疫反应。我们将测试我们的 假说：1)确定Sp混合感染对宿主对IAV感染的抵抗力/易感性的影响，2) 研究炎性反应在LAV/Sp混合感染中介导保护或免疫病理的作用， 3)确定Sp混合感染对CDS T细胞对IAV和LAV特异性CDS T反应的影响 细胞记忆。在本研究的最后，我们希望对复杂的宿主--病毒有一个更好的了解 在合并感染期间发生的相互作用，目标是开发干预措施，使 平衡互动，使东道主受益。