Douville Renée N, Bastien Nathalie, Li Yan, Pochard Pierre, Simons F Estelle R, HayGlass Kent T
Department of Immunology, University of Manitoba, 730 William Avenue, Winnipeg, Manitoba, Canada.
J Immunol. 2006 May 15;176(10):5848-55. doi: 10.4049/jimmunol.176.10.5848.
Human metapneumovirus (MPV) is a recently discovered pathogen that causes repeated lower respiratory tract infections beginning in infancy. The prevalence, nature and control of human regulatory responses to MPV are unknown. In this study, we develop and optimize systems to evaluate MPV-driven cytokine responses. Using primary culture of human PBMC from previously exposed adults, MPV-stimulated responses were directly compared with those elicited by genetically and clinically similar respiratory syncytial virus (RSV). Intense IL-6 production was evident following culture with infectious or inactivated RSV. MPV elicited IL-6 responses averaging 3.5-fold more intense (p < 0.001). Virus-dependent expression of IL-11, IL-12, IFN-alpha, and other innate immunity cytokines differed little between MPV and RSV. When examining adaptive immunity, RSV infection elicited strong IFN-gamma responses by all 60 adults. In marked contrast, MPV elicited IFN-gamma in a lower frequency of adults (p < 0.002) and at levels averaging 6-fold weaker (p < 0.001). These Th1-dominated responses were CD4, CD8, CD86 dependent, and were closely paralleled by strong virus-driven IL-10 and CCL5 production. For MPV and RSV, Th2 (IL-5, IL-13) responses were sporadic, occurring in 10-40% of the population. Thus, MPV and RSV, although both ubiquitous and leading to very high levels of infection, seroconversion, and clinically similar presentation in the population, evoke distinct innate and adaptive T cell-dependent cytokine responses. Although both viruses yield Th1-dominated responses with strong IL-10 and CCL5 production, MPV restimulation results in markedly more robust IL-6 and significantly weaker adaptive cytokine responses, in both prevalence and intensity, than does RSV.
人偏肺病毒（MPV）是一种最近发现的病原体，可导致婴儿期反复发生下呼吸道感染。人体对MPV的调节反应的普遍性、性质和控制尚不清楚。在本研究中，我们开发并优化了评估MPV驱动的细胞因子反应的系统。使用先前接触过的成年人的人外周血单核细胞（PBMC）原代培养物，将MPV刺激的反应与由基因和临床相似的呼吸道合胞病毒（RSV）引发的反应直接进行比较。用感染性或灭活的RSV培养后，明显产生强烈的IL-6。MPV引发的IL-6反应平均强度高3.5倍（p<0.001）。MPV和RSV之间，IL-11、IL-12、IFN-α和其他先天免疫细胞因子的病毒依赖性表达差异不大。在检查适应性免疫时，RSV感染在所有60名成年人中均引发强烈的IFN-γ反应。与之形成鲜明对比的是，MPV在较低比例的成年人中引发IFN-γ（p<0.002），且水平平均弱6倍（p<0.001）。这些以Th1为主的反应依赖于CD4、CD8、CD86，并且与强烈的病毒驱动的IL-10和CCL5产生密切平行。对于MPV和RSV，Th2（IL-5、IL-13）反应是散发性的，发生在10%-40%的人群中。因此，MPV和RSV虽然在人群中都无处不在，导致非常高的感染水平、血清转化和临床相似表现，但会引发不同的先天和适应性T细胞依赖性细胞因子反应。虽然两种病毒都产生以Th1为主的反应，并伴有强烈的IL-10和CCL5产生，但与RSV相比，MPV再刺激导致IL-6明显更强，而适应性细胞因子反应在发生率和强度上均明显较弱。
