Lee Debbie C P, Tay Neil Q, Thian Marini, Prabhu Nayana, Furuhashi Kazuki, Kemeny David M
Immunology Programme, Department of Microbiology and Immunology, Centre for Life Sciences, National University of Singapore, Singapore.
PLoS One. 2018 Jan 2;13(1):e0190063. doi: 10.1371/journal.pone.0190063. eCollection 2018.
Influenza and asthma are two of the major public health concerns in the world today. During the 2009 influenza pandemic asthma was found to be the commonest comorbid illness of patients admitted to hospital. Unexpectedly, it was also observed that asthmatic patients admitted to hospital with influenza infection were less likely to die or require admission to intensive care compared with non-asthmatics. Using an in vivo model of asthma and influenza infection we demonstrate that prior exposure to Blomia tropicalis extract (BTE) leads to an altered immune response to influenza infection, comprised of less severe weight loss and faster recovery following infection. This protection was associated with significant increases in T cell numbers in the lungs of BTE sensitised and infected mice, as well as increased IFN-γ production from these cells. In addition, elevated numbers of CD11b+ dendritic cells (DCs) were found in the lung draining lymph nodes following infection of BTE sensitised mice compared to infected PBS treated mice. These CD11b+ DCs appeared to be better at priming CD8 specific T cells both in vivo and ex vivo, a function not normally attributed to CD11b+ DCs. We propose that this alteration in cross-presentation and more efficient T cell priming seen in BTE sensitised mice, led to the earlier increase in T cells in the lungs and subsequently faster clearance of the virus and reduced influenza induced pathology. We believe this data provides a novel mechanism that explains why asthmatic patients may present with less severe disease when infected with influenza.
流感和哮喘是当今世界两大主要的公共卫生问题。在2009年流感大流行期间,哮喘被发现是住院患者最常见的合并症。出乎意料的是,还观察到与非哮喘患者相比,因流感感染住院的哮喘患者死亡或需要入住重症监护病房的可能性较小。使用哮喘和流感感染的体内模型,我们证明预先接触热带嗜卷书虱提取物(BTE)会导致对流感感染的免疫反应发生改变,表现为感染后体重减轻较轻且恢复较快。这种保护作用与BTE致敏并感染的小鼠肺部T细胞数量显著增加以及这些细胞产生的IFN-γ增加有关。此外,与感染PBS处理的小鼠相比,BTE致敏小鼠感染后在肺引流淋巴结中发现CD11b +树突状细胞(DC)数量增加。这些CD11b + DC在体内和体外似乎都更擅长启动CD8特异性T细胞,这一功能通常不归因于CD11b + DC。我们提出,在BTE致敏小鼠中看到的交叉呈递改变和更有效的T细胞启动导致肺部T细胞更早增加,随后病毒清除更快,流感诱导的病理变化减少。我们相信这些数据提供了一种新机制,解释了为什么哮喘患者感染流感时病情可能较轻。