Neonatal LPS Administered Before Sensitization Reduced the Number of Inflammatory Monocytes and Abrogated the Development of OVA-Induced Th2 Allergic Airway Inflammation.
Neonatal LPS Administered Before Sensitization Reduced the Number of Inflammatory Monocytes and Abrogated the Development of OVA-Induced Th2 Allergic Airway Inflammation.
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致敏前给予新生儿 LPS 可减少炎症单核细胞的数量并消除 OVA 诱导的 Th2 过敏性气道炎症的发展
DOI：
10.3389/fimmu.2021.725906
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发表时间：
2021
影响因子：
7.3
通讯作者：
Han J
中科院分区：
文献类型：
--
作者：
Gao L;Wu M;Liu H;He M;Jiang H;Shang R;Wang Q;Song Z;Huang Y;Han J
越来越清楚的是，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，传统农场是最强的保护环境之一，其保护作用至少部分归因于农场高水平的脂多糖(LPS)暴露。然而，其潜在的机制仍不清楚，特别是在卵蛋白(OVA)诱导的新生儿过敏性哮喘模型中。在这里，我们在两个年龄组中使用了OVA诱导的哮喘模型，分别是新生小鼠和成年小鼠，分别用OVA/明矾腹膜致敏。在卵清蛋白/明矾致敏前，于腹腔内注射脂多糖。测定并比较两个年龄组大鼠肺内过敏性气道炎症和腹膜免疫环境的变化。我们发现，在新生儿组中，内毒素治疗阻止了Th2过敏性呼吸道反应的发展。在成年组，内毒素治疗后Th2过敏反应减轻，伴有Th17反应和中性粒细胞浸润。我们进一步研究了腹膜腔内的免疫环境，以阐明这种年龄相关差异的潜在机制。我们的数据显示，在新生小鼠中，内毒素治疗显著减少了腹腔炎性单核细胞的数量。在成年组，内毒素处理使这些细胞的功能发生改变，这与Th1和Th17的极化有关。我们的结果提供了更多的证据，表明早期生命的免疫不同于成人，特别是在腹膜腔内，并强调了对过敏性哮喘进行干预的时机的重要性。我们的结果表明，生命早期的内毒素治疗对Th2过敏反应的发生具有保护作用。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。
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.
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影响因子：
4.4
作者：
Nowroozilarki, Negar;Oez, Hasan Halit;Kolahian, Saeed
通讯作者：
Kolahian, Saeed
DOI：
10.4049/jimmunol.0900164
发表时间：
2009-10-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
McKee AS;Munks MW;MacLeod MK;Fleenor CJ;Van Rooijen N;Kappler JW;Marrack P
通讯作者：
Marrack P
低剂量 LPS 诱导哮喘耐受性 Treg 偏差
影响因子：
7.3
作者：
Ding F;Liu B;Niu C;Wang T;Wang Y;Geng G;Tian D;Dai J;Fu Z
通讯作者：
Fu Z
影响因子：
32.4
作者：
Plantinga, Maud;Guilliams, Martin;Lambrecht, Bart N.
通讯作者：
Lambrecht, Bart N.
影响因子：
4.4
作者：
Basha S;Surendran N;Pichichero M
通讯作者：
Pichichero M