Maternal TLR signaling is required for prenatal asthma protection by the nonpathogenic microbe Acinetobacter lwoffii F78.
Maternal TLR signaling is required for prenatal asthma protection by the nonpathogenic microbe Acinetobacter lwoffii F78.
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DOI：
10.1084/jem.20090845
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发表时间：
2009-12-21
期刊：
影响因子：
--
通讯作者：
Renz H
中科院分区：
文献类型：
--
作者：
Conrad ML;Ferstl R;Teich R;Brand S;Blümer N;Yildirim AO;Patrascan CC;Hanuszkiewicz A;Akira S;Wagner H;Holst O;von Mutius E;Pfefferle PI;Kirschning CJ;Garn H;Renz H
产前和产后环境可能是预防过敏和哮喘的机会窗口，卫生假说意味着微生物制剂可能在这方面发挥重要作用。本研究使用牛棚来源的细菌鲁氏不动杆菌 F78 和实验性过敏性气道炎症小鼠模型，研究了卫生假设、母体（产前）微生物暴露以及 Toll 样受体 (TLR) 信号在产前预防哮喘中的作用。母亲鼻内暴露于 A. lwoffii F78 可防止后代发生实验性哮喘。母体方面，A. lwoffii F78 暴露导致肺和血清促炎细胞因子产生短暂增加以及肺 TLR 信使 RNA 上调。相反，在胎盘组织中观察到 TLR 的抑制。为了进一步研究，在 TLR2/3/4/7/9−/− 敲除小鼠中测试了母体 TLR 信号传导的功能相关性。在用 A. lwoffii F78 处理的 TLR2/3/4/7/9−/− 纯合母鼠的杂合子后代中，哮喘预防作用完全消失。此外，这些暴露于 A. lwoffii F78 的母亲也没有出现轻微的局部和全身炎症反应。这些数据建立了母体细菌暴露、功能性母体 TLR 信号传导和后代哮喘保护之间的直接关系。
The pre- and postnatal environment may represent a window of opportunity for allergy and asthma prevention, and the hygiene hypothesis implies that microbial agents may play an important role in this regard. Using the cowshed-derived bacterium Acinetobacter lwoffii F78 together with a mouse model of experimental allergic airway inflammation, this study investigated the hygiene hypothesis, maternal (prenatal) microbial exposure, and the involvement of Toll-like receptor (TLR) signaling in prenatal protection from asthma. Maternal intranasal exposure to A. lwoffii F78 protected against the development of experimental asthma in the progeny. Maternally, A. lwoffii F78 exposure resulted in a transient increase in lung and serum proinflammatory cytokine production and up-regulation of lung TLR messenger RNA. Conversely, suppression of TLRs was observed in placental tissue. To investigate further, the functional relevance of maternal TLR signaling was tested in TLR2/3/4/7/9−/− knockout mice. The asthma-preventive effect was completely abolished in heterozygous offspring from A. lwoffii F78–treated TLR2/3/4/7/9−/− homozygous mother mice. Furthermore, the mild local and systemic inflammatory response was also absent in these A. lwoffii F78–exposed mothers. These data establish a direct relationship between maternal bacterial exposures, functional maternal TLR signaling, and asthma protection in the progeny.
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影响因子：
2.8
作者：
Neuhaus-Steinmetz, U;Glaab, T;Renz, H
通讯作者：
Renz, H
DOI：
10.1073/pnas.1934678100
发表时间：
2003-09-16
影响因子：
11.1
作者：
Honda, K;Sakaguchi, S;Taniguchi, T
通讯作者：
Taniguchi, T
影响因子：
14.2
作者：
Ege, MJ;Bieli, C;Braun-Fahrländer, C
通讯作者：
Braun-Fahrländer, C
影响因子：
14.2
作者：
Sel, Serdar;Wegmann, Michael;Garn, Holger
通讯作者：
Garn, Holger
影响因子：
14.2
作者：
Debarry, Jennifer;Garn, Holger;Heine, Holger
通讯作者：
Heine, Holger