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.

越来越清楚的是，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。其中，传统农场是保护性最强的环境之一，其保护作用至少部分归因于农场对脂多糖 (LPS) 的高水平暴露。然而，潜在的机制仍然难以捉摸，尤其是在卵清蛋白 (OVA) 诱导的新生儿过敏性哮喘模型中。在这里，我们在两个年龄组（新生儿和成人）中使用 OVA 诱导的哮喘模型，当小鼠首先分别以新生儿和成人的腹膜 OVA/明矾致敏时。在 OVA/明矾致敏之前将 LPS 注入腹腔。确定并比较了这两个年龄组之间 LPS 治疗对肺部过敏性气道炎症和腹膜腔免疫环境的影响。我们发现 LPS 治疗消除了新生儿组 Th2 过敏性气道反应的发展。在成人组中，改善的 Th2 过敏反应伴随着 LPS 治疗后的 Th17 反应和中性粒细胞浸润。我们进一步研究了腹腔中的免疫环境，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 治疗显着减少了腹腔中炎症单核细胞的数量。在成人组中，LPS 治疗改变了这些与 Th1 和 Th17 极化相关的细胞的功能。我们的研究结果提供了更多证据表明生命早期的免疫与成人不同，尤其是在腹膜腔中，并强调了干预过敏性哮喘的时机的重要性。我们的研究结果表明，生命早期的 LPS 治疗对 Th2 过敏反应的发展具有保护作用。另一方面，当抑制成年小鼠的 Th2 反应时，它可能会导致更严重的哮喘表型。