Division of ENT Diseases, CLINTEC, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
PLoS One. 2012;7(2):e32110. doi: 10.1371/journal.pone.0032110. Epub 2012 Feb 15.
Bacterial and viral infections are known to promote airway hyperresponsiveness (AHR) in asthmatic patients. The mechanism behind this reaction is poorly understood, but pattern recognizing Toll-like receptors (TLRs) have recently been suggested to play a role.
To explore the relation between infection-induced airway inflammation and the development of AHR, poly(I:C) activating TLR3 and LPS triggering TLR4, were chosen to represent viral and bacterial induced interactions, respectively. Female BALB/c or MyD88-deficient C57BL/6 mice were treated intranasally with either poly(I:C), LPS or PBS (vehicle for the control group), once a day, during 4 consecutive days.
When methacholine challenge was performed on day 5, BALB/c mice responded with an increase in airway resistance. The maximal resistance was higher in the poly(I:C) and LPS treated groups than among the controls, indicating development of AHR in response to repeated TLR activation. The proportion of lymphocytes in broncheoalveolar lavage fluid (BALF) increased after poly(I:C) treatment whereas LPS enhanced the amount of neutrophils. A similar cellular pattern was seen in lung tissue. Analysis of 21 inflammatory mediators in BALF revealed that the TLR response was receptor-specific. MyD88-deficient C57BL/6 mice responded to poly (I:C) with an influx of lymphocytes, whereas LPS caused no inflammation.
In vivo activation of TLR3 and TLR4 in BALB/c mice both caused AHR in conjunction with a local inflammatory reaction. The AHR appeared to be identical regardless of which TLR that was activated, whereas the inflammation exhibited a receptor specific profile in terms of both recruited cells and inflammatory mediators. The inflammatory response caused by LPS appeared to be dependent on MyD88 pathway. Altogether the presented data indicate that the development of AHR and the induction of local inflammation might be the result of two parallel events, rather than one leading to another.
细菌和病毒感染已知可促进哮喘患者的气道高反应性（AHR）。这种反应的机制尚不清楚，但最近有人提出模式识别 Toll 样受体（TLR）可能起作用。
为了探讨感染引起的气道炎症与 AHR 发展之间的关系，选择聚（I：C）激活 TLR3 和 LPS 触发 TLR4 分别代表病毒和细菌诱导的相互作用。雌性 BALB/c 或 MyD88 缺陷型 C57BL/6 小鼠每天接受一次鼻腔内给予聚（I：C）、LPS 或 PBS（对照组的载体），连续 4 天。
当在第 5 天进行乙酰甲胆碱挑战时，BALB/c 小鼠的气道阻力增加。聚（I：C）和 LPS 处理组的最大阻力高于对照组，表明 TLR 反复激活后 AHR 的发展。支气管肺泡灌洗液（BALF）中的淋巴细胞比例在聚（I：C）处理后增加，而 LPS 则增加了中性粒细胞的数量。在肺组织中也观察到类似的细胞模式。BALF 中 21 种炎症介质的分析表明，TLR 反应是受体特异性的。MyD88 缺陷型 C57BL/6 小鼠对聚（I：C）的反应是淋巴细胞的涌入，而 LPS 则没有引起炎症。
在 BALB/c 小鼠体内激活 TLR3 和 TLR4 均引起 AHR 伴局部炎症反应。AHR 似乎与激活的 TLR 无关，而炎症在募集的细胞和炎症介质方面表现出受体特异性特征。LPS 引起的炎症反应似乎依赖于 MyD88 途径。总的来说，所提供的数据表明，AHR 的发展和局部炎症的诱导可能是两个平行事件的结果，而不是一个导致另一个。
