Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Front Immunol. 2021 Sep 22;12:725906. doi: 10.3389/fimmu.2021.725906. eCollection 2021.
It is becoming increasingly clear that environment factors during early life play a pivotal role in the development of allergic asthma. Among these, a traditional farm is one of the strongest protective environments, and the protective effects have been, at least in part, attributed to the high-level exposure to lipopolysaccharide (LPS) on farms. However, the underlying mechanisms remain elusive, especially in ovalbumin (OVA)-induced neonatal allergic asthma model. Here, we used the OVA-induced asthma model in two age groups, neonatal and adult, when mice were first sensitized with peritoneal OVA/alum as neonates and adults, respectively. LPS was injected in the peritoneal cavity before OVA/alum sensitization. The effects of LPS treatment on allergic airway inflammation in the lung and the immune milieu in the peritoneal cavity were determined and compared between these two age groups. We found that LPS treatment abrogated the development of Th2 allergic airway responses in the neonatal group. In the adult group, the ameliorated Th2 allergic responses were accompanied with Th17 responses and neutrophil infiltration upon LPS treatment. We further investigated the immune milieu in the peritoneal cavity to elucidate the underlying mechanisms of this age-dependent difference. Our data show that in neonatal mice, LPS treatment significantly reduced the number of inflammatory monocytes in the peritoneal cavity. In the adult group, LPS treatment shifted the function of these cells which associated with Th1 and Th17 polarization. Our results provide more evidence that immunity in early life is distinct from that in adults, especially in the peritoneal cavity, and emphasize the importance of timing for the intervention of allergic asthma. Our results suggest that LPS treatment during early life is protective for the development of Th2 allergic responses. On the other hand, it might lead to a more severe phenotype of asthma when dampening the Th2 responses in adult mice.
越来越明显的是，生命早期的环境因素在过敏性哮喘的发展中起着关键作用。在这些因素中，传统农场是最强的保护环境之一，其保护作用至少部分归因于农场中高水平的脂多糖 (LPS) 暴露。然而，潜在机制仍不清楚，特别是在卵清蛋白 (OVA) 诱导的新生过敏性哮喘模型中。在这里，我们使用了两个年龄组的 OVA 诱导的哮喘模型，即新生和成年组，当小鼠分别在新生和成年时首次用腹膜内 OVA/明矾致敏时。在 OVA/明矾致敏前，将 LPS 注入腹腔。确定并比较了 LPS 处理对肺中过敏性气道炎症和腹腔免疫环境的影响。我们发现 LPS 处理消除了新生组 Th2 过敏性气道反应的发展。在成年组中，LPS 处理改善的 Th2 过敏性反应伴随着 Th17 反应和中性粒细胞浸润。我们进一步研究了腹腔免疫环境，以阐明这种年龄依赖性差异的潜在机制。我们的数据表明，在新生小鼠中，LPS 处理显著减少了腹腔中的炎性单核细胞数量。在成年组中，LPS 处理改变了这些细胞的功能，与 Th1 和 Th17 极化相关。我们的结果提供了更多证据表明，生命早期的免疫与成年后的免疫不同，特别是在腹腔中，并且强调了干预过敏性哮喘的时机的重要性。我们的结果表明，生命早期的 LPS 处理对 Th2 过敏性反应的发展具有保护作用。另一方面，它可能会导致成年小鼠中抑制 Th2 反应时更严重的哮喘表型。
