Response to Rhinovirus Infection by Human Airway Epithelial Cells and Peripheral Blood Mononuclear Cells in an In Vitro Two-Chamber Tissue Culture System
Response to Rhinovirus Infection by Human Airway Epithelial Cells and Peripheral Blood Mononuclear Cells in an In Vitro Two-Chamber Tissue Culture System
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DOI：
10.1371/journal.pone.0066600
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发表时间：
2013-06-17
期刊：
影响因子：
3.7
通讯作者：
Anderson, Larry J.
中科院分区：
文献类型：
--
作者：
Rajan, Devi;Gaston, Kelsey A.;Anderson, Larry J.
人鼻病毒（HRV）感染与普通感冒有关，偶尔与更严重的下呼吸道疾病有关，经常与哮喘恶化有关。HRV感染的临床特征及其与哮喘急性发作的相关性表明，某些HRV疾病是由病毒诱导的宿主对感染的免疫反应引起的。为了研究HRV感染诱导的宿主反应和这些反应对疾病的贡献，我们已经开发了一种体外模型，HRV感染的人气道上皮细胞（Calu-3细胞）和随后暴露的人外周血单核细胞（PBMC），这些感染的细胞在一个双室trans-well组织培养系统。使用该模型，我们研究了HRV 14（种B）和HRV 16（种A）诱导的细胞因子和趋化因子反应与PBMC从四个健康成人。用任一种病毒感染Calu-3细胞诱导HRV相关的FGF-碱性、IL-15、IL-6、IL-28 A、ENA-78和IP-10增加。与模拟感染的细胞相比，向HRV 14感染的细胞中加入PBMC使MIP-1 β、IL-28 A、MCP-2和IFN-α显著增加。有趣的是，ENA-78水平在暴露于PBMC的HRV 14感染的细胞中降低。向HRV 16感染的细胞中加入PBMC既不能有效诱导MIP-1 β、IL-28 A和IFN-α，也不能降低ENA-78水平。我们的研究结果表明HRV 14和HRV 16与PBMC来源之间在上调或下调几种细胞因子（包括与气道炎症相关的细胞因子）方面存在明显差异。这种差异可能是与不同HRV种类相关的疾病变化的原因之一，包括其他研究表明的与哮喘急性发作相关的变化。进一步研究与来自不同患者组的不同HRV和PBMC相关的免疫应答以及导致这些差异的机制，应有助于表征HRV疾病的发病机制并产生新的治疗方法。
Human rhinovirus (HRV) infections are associated with the common cold, occasionally with more serious lower respiratory tract illnesses, and frequently with asthma exacerbations. The clinical features of HRV infection and its association with asthma exacerbation suggest that some HRV disease results from virus-induced host immune responses to infection. To study the HRV-infection-induced host responses and the contribution of these responses to disease, we have developed an in vitro model of HRV infection of human airway epithelial cells (Calu-3 cells) and subsequent exposure of human peripheral blood mononuclear cells (PBMCs) to these infected cells in a two-chamber trans-well tissue culture system. Using this model, we studied HRV 14 (species B) and HRV 16 (species A) induced cytokine and chemokine responses with PBMCs from four healthy adults. Infection of Calu-3 cells with either virus induced HRV-associated increases in FGF-Basic, IL-15, IL-6, IL-28A, ENA-78 and IP-10. The addition of PBMCs to HRV 14-infected cells gave significant increases in MIP-1 beta, IL-28A, MCP-2, and IFN-alpha as compared with mock-infected cells. Interestingly, ENA-78 levels were reduced in HRV 14 infected cells that were exposed to PBMCs. Addition of PBMCs to HRV 16-infected cells did not induce MIP-1 beta, IL-28A and IFN-alpha efficiently nor did it decrease ENA-78 levels. Our results demonstrate a clear difference between HRV 14 and HRV 16 and the source of PBMCs, in up or down regulation of several cytokines including those that are linked to airway inflammation. Such differences might be one of the reasons for variation in disease associated with different HRV species including variation in their link to asthma exacerbations as suggested by other studies. Further study of immune responses associated with different HRVs and PBMCs from different patient groups, and the mechanisms leading to these differences, should help characterize pathogenesis of HRV disease and generate novel approaches to its treatment.