Inflammation and Therapy for Respiratory Virus Infection

今年，我与纽约州立大学北部医科大学和澳大利亚纽卡斯尔大学的合作者一起，撰写了两份描述翻译进展的原创报告。 在这些研究的第一个，我们检查了老年人的炎症反应，但在其他免疫幼稚小鼠感染小鼠肺炎病毒（PVM）。 虽然我们没有看到病毒复制的程度或动力学的变化，但我们观察到局部炎症介质的产生减少。 促炎介质的产生依赖于血小板减少，与粒细胞募集减少和临床反应严重程度降低相关，包括体重减轻和呼吸功能障碍。 将这些结果与老年人受试者中报告的结果进行比较时观察到的差异可能与衰老的具体程度及其对生化和细胞炎症反应的影响和/或终生病毒再暴露对急性肺炎病毒病临床结局的作用有关（Bonville et al. Virology 2007）。 在第二项研究中，我们探索了嗜酸性粒细胞在用于小鼠鼻内激发模型时在促进清除流行的呼吸道病原体呼吸道合胞病毒（RSV）中发挥直接作用的可能性。具体来说，我们发现，病毒从肺组织中的清除是更迅速的嗜酸性粒细胞增多（白细胞介素-5转基因）小鼠比野生型小鼠。在机制方面，我们证明了嗜酸性粒细胞表达识别病毒核酸的TLR，在TLR 7-MyD 88途径的ssRNA刺激后被激活和去活化。总的来说，结果表明，嗜酸性粒细胞促进病毒清除，从而可能限制病毒诱导的肺功能障碍。（Phipps等人，Blood 2007）。 我还发表了一篇描述小鼠模型肺炎病毒的邀请同行评审手稿，题为“肺炎病毒或小鼠：自然宿主中的严重呼吸道病毒感染”（Immunol Lett 2008; 118：6 - 12）

This year, together with collaborators at SUNY Upstate Medical University, New York and University of Newcastle, Australia, I have contributed to two original reports describing translational advances. In the first of these studies, we examined the inflammatory responses of older, but otherwise immunologically naive mice to infection with pneumonia virus of mice (PVM). Although we see no changes in the extent or kinetics of virus replication, we observe diminished local production of inflammatory mediators. Age-dependent diminished production of proinflammatory mediators was associated with diminished recruitment of granulocytes and reduced severity of clinical responses, including weight loss and respiratory dysfunction. The differences observed when comparing these results to those reported among elderly human subjects may be related to the specific extent of aging and its impact on biochemical and cellular inflammatory responses and/or the role of lifetime virus re-exposure on the clinical outcome from acute pneumovirus disease (Bonville et al. Virology 2007). In a second study, we explored the possibility that eosinophils play a direct role in promoting clearance of the prevalent respiratory pathogen, respiratory syncytial virus (RSV) when used in an intranasal challenge model in mice. Specifically, we found that virus clearance from lung tissue was more rapid in hypereosinophilic (interleukin-5 transgenic) mice than in wild type mice. In terms of mechanism, we demonstrated that eosinophils express TLRs that recognize viral nucleic acids, are activated and degranulate after ssRNA stimulation of the TLR7-MyD88 pathway. Collectively, the results demonstrate that eosinophils promote virus clearance and may thus limit virus-induced lung dysfunction. (Phipps et al. Blood 2007). I have also published an invited, peer-reviewed manuscript describing the pneumonia virus of mice model entitled "Pneumonia virus or mice: severe respiratory virus infection in a natural host" (Immunol Lett 2008; 118: 6 - 12)