Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan, China.
Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, China.
Cell Mol Immunol. 2021 Feb;18(2):472-483. doi: 10.1038/s41423-020-00621-4. Epub 2021 Jan 13.
Virus-induced asthma is prevalent among children, but its underlying mechanisms are unclear. Accumulated evidence indicates that early-life respiratory virus infection increases susceptibility to allergic asthma. Nonetheless, the relationship between systemic virus infections, such as enterovirus infection, and the ensuing effects on allergic asthma development is unknown. Early-life enterovirus infection was correlated with higher risks of allergic diseases in children. Adult mice exhibited exacerbated mite allergen-induced airway inflammation following recovery from EV-A71 infection in the neonatal period. Bone marrow-derived macrophages (BMDMs) from recovered EV-A71-infected mice showed sustained innate immune memory (trained immunity) that could drive naïve T helper cells toward Th2 and Th17 cell differentiation when in contact with mites. Adoptive transfer of EV-A71-trained BMDMs induced augmented allergic inflammation in naïve recipient mice, which was inhibited by 2-deoxy-D-glucose (2-DG) pretreatment, suggesting that trained macrophages following enterovirus infection are crucial in the progression of allergic asthma later in life.
病毒诱发的哮喘在儿童中较为常见，但其潜在机制尚不清楚。越来越多的证据表明，生命早期的呼吸道病毒感染会增加过敏性哮喘的易感性。然而，全身病毒感染（如肠道病毒感染）与随后对过敏性哮喘发展的影响之间的关系尚不清楚。生命早期的肠道病毒感染与儿童患过敏性疾病的风险增加有关。成年小鼠在新生儿期从 EV-A71 感染中恢复后，对螨过敏原诱导的气道炎症表现出加重。从已恢复 EV-A71 感染的小鼠中分离出的骨髓来源的巨噬细胞（BMDMs）表现出持续的固有免疫记忆（训练免疫），当与螨虫接触时，这种记忆可以促使幼稚 T 辅助细胞向 Th2 和 Th17 细胞分化。EV-A71 训练的 BMDMs 的过继转移会在幼稚受体小鼠中引起增强的过敏炎症，这种炎症可被 2-脱氧-D-葡萄糖（2-DG）预处理抑制，这表明在生命后期，肠道病毒感染后的训练巨噬细胞在过敏性哮喘的进展中至关重要。
