Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan.
Department of Medicine, School of Medicine, Chang Gung University, Taipei, Taiwan.
Immun Inflamm Dis. 2021 Mar;9(1):183-195. doi: 10.1002/iid3.376. Epub 2020 Nov 25.
Toll-like receptor (TLR)-7-associated rhinovirus (RV) activation is involved in the pathogenesis of asthma. Plasmacytoid dendritic cells (pDCs) are the main interferon-α-producing cells against viruses.
To determine whether asthmatic patients and control subjects differ in terms of interferon-α expression in pDCs under TLR-7 or RV stimulation.
pDCs were identified in BDCA-2+ and HLA-DR+ peripheral blood mononuclear cells. Interferon-α expression of pDCs was analyzed after TLR-7 stimulation with or without interleukin 4 (IL-4)/IL-13 pretreatment. Interferon-α expression was also analyzed after RV stimulation over periods of 24, 48, or 96 h with or without IL-4 pretreatment. RV detection and molecular typing were assayed from throat swabs.
Following TLR-7 stimulation, the expression of intracellular interferon-α was higher in the pDCs of normal subjects than those of asthmatic patients; however, pretreatment with IL-4 was shown to reduce this effect. After 48- and 96-h RV stimulation, we observed a notable increase in the production of interferon-α of pDCs in normal subjects but not in asthmatic patients. Baseline interferon-α expression in pDCs and the incidence of asthma exacerbation to emergency was higher among the 13% of patients identified as rhinovirus+ than among their RV counterparts.
Our study discovered the response to TLR-7 stimulation in pDCs was compromised and the sustainability of interferon-α expression to RV stimulation was reduced in pDCs of asthmatic patients, which provide further evidence of defective innate response and subspeciality to RV infection in asthma. The high exacerbation history founded in RV+ patients agrees with these findings. Further research is required for the modulatory effect of IL-4 on TLR-7 stimulated pDCs.
Toll 样受体 (TLR)-7 相关鼻病毒 (RV) 激活参与哮喘的发病机制。浆细胞样树突状细胞 (pDC) 是针对病毒产生干扰素-α的主要细胞。
确定哮喘患者和对照者在 TLR-7 或 RV 刺激下 pDC 中干扰素-α表达是否存在差异。
在 BDCA-2+和 HLA-DR+外周血单核细胞中鉴定 pDC。分析 TLR-7 刺激后 pDC 中干扰素-α的表达，以及 IL-4/IL-13 预处理前后的表达。还分析了 RV 刺激 24、48 或 96 小时后 pDC 中干扰素-α的表达，以及 IL-4 预处理前后的表达。从咽喉拭子中检测 RV 并进行分子分型。
TLR-7 刺激后，正常受试者 pDC 内细胞内干扰素-α的表达高于哮喘患者；然而，IL-4 预处理可降低这种作用。RV 刺激 48 至 96 小时后，我们观察到正常受试者 pDC 中干扰素-α的产生明显增加，但哮喘患者则没有。在确定为鼻病毒+的 13%患者中，pDC 中 IFN-α的基础表达和急诊哮喘加重的发生率高于其 RV 对应物。
我们的研究发现，哮喘患者 pDC 对 TLR-7 刺激的反应受损，pDC 对 RV 刺激的干扰素-α表达可持续性降低，这进一步证明了哮喘患者先天反应缺陷和对 RV 感染的特殊性。在 RV+患者中发现的高加重病史与这些发现一致。需要进一步研究 IL-4 对 TLR-7 刺激的 pDC 的调节作用。
