Division of Pediatric Infectious Diseases, Department of Pediatrics, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan.
Division of Pediatric Infectious Diseases, Department of Pediatrics, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Pediatrics, Chi-Mei Medical Center, Tainan, Taiwan.
J Microbiol Immunol Infect. 2019 Apr;52(2):207-214. doi: 10.1016/j.jmii.2018.08.010. Epub 2018 Aug 31.
Adenovirus infections are very common in children and sometimes fatal. Immune responses and hypercytokinemia are related to disease severity in patients with adenovirus infection. Understanding of viral replication and immune responses could help elucidate the immunopathogenesis of severe adenovirus infections.
Polarized human airway epithelial cells (hAECs) were set up to mimic human airway, and we conducted high (1 the multiplicity of infection, MOI) and low dosage (0.5 MOI) of wild-type adenovirus serotype 3 infection in hAECs from both apical (AP) and basolateral (BL) compartments, compared the viral replication kinetics and measured 25 cytokine and 9 chemokine levels by multiplex immunoassay to evaluate the host immune response.
Virus titer was the highest in the apical compartment in low dose apical infection. BL infection showed a relative steady viral titer in different doses and infection sites. Responses of several cytokines such as IL-1RA, IL-21 and all of the chemokines were found after adenovirus infection. Besides, the responses detected in the BL compartment were generally higher than those in the apical compartment, especially IL-1RA, IL-21, GM-CSF, GRO-α, SDF-1α and IL-8.
During the infections of hAECs by adenovirus, higher viral replication was found in the apical compartment but cytokine and chemokine responses were higher in the basolateral compartment. This indicated viral entrance and replication occurred more in the apical part and major innate response took place in the basolateral part, which may make adenovirus infect human airway efficiently and cause different degree of severity.
腺病毒感染在儿童中非常常见，有时甚至是致命的。免疫反应和细胞因子血症与腺病毒感染患者的疾病严重程度有关。了解病毒复制和免疫反应有助于阐明严重腺病毒感染的免疫发病机制。
建立极化的人气道上皮细胞（hAEC）以模拟人气道，我们在 hAEC 中进行高（1 感染复数，MOI）和低剂量（0.5 MOI）野生型腺病毒血清型 3 感染，比较病毒复制动力学，并通过多重免疫分析测量 25 种细胞因子和 9 种趋化因子水平，以评估宿主免疫反应。
低剂量感染时，病毒滴度在顶端隔室最高。BL 感染在不同剂量和感染部位表现出相对稳定的病毒滴度。腺病毒感染后会检测到几种细胞因子（如 IL-1RA、IL-21 和所有趋化因子）的反应。此外，BL 隔室中检测到的反应通常高于顶端隔室，特别是 IL-1RA、IL-21、GM-CSF、GRO-α、SDF-1α 和 IL-8。
在 hAEC 感染腺病毒期间，顶端隔室中的病毒复制较高，但 BL 隔室中的细胞因子和趋化因子反应较高。这表明病毒进入和复制发生在顶端部分更多，而主要的先天反应发生在 BL 部分，这可能使腺病毒有效地感染人气道并引起不同程度的严重程度。
