Rodríguez Dunia, Keller Alexandre C, Faquim-Mauro Eliana L, de Macedo Mahasti S, Cunha Fernando Q, Lefort Jean, Vargaftig B Boris, Russo Momtchilo
Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil.
J Immunol. 2003 Jul 15;171(2):1001-8. doi: 10.4049/jimmunol.171.2.1001.
Asthma results from an intrapulmonary allergen-driven Th2 response and is characterized by intermittent airway obstruction, airway hyperreactivity, and airway inflammation. An inverse association between allergic asthma and microbial infections has been observed. Microbial infections could prevent allergic responses by inducing the secretion of the type 1 cytokines, IL-12 and IFN-gamma. In this study, we examined whether administration of bacterial LPS, a prototypic bacterial product that activates innate immune cells via the Toll-like receptor 4 (TLR4) could suppress early and late allergic responses in a murine model of asthma. We report that LPS administration suppresses the IgE-mediated and mast cell-dependent passive cutaneous anaphylaxis, pulmonary inflammation, airway eosinophilia, mucus production, and airway hyperactivity. The suppression of asthma-like responses was not due to Th1 shift as it persisted in IL-12(-/-) or IFN-gamma(-/-) mice. However, the suppressive effect of LPS was not observed in TLR4- or NO synthase 2-deficient mice. Our findings demonstrate, for the first time, that LPS suppresses Th2 responses in vivo via the TLR4-dependent pathway that triggers NO synthase 2 activity.
哮喘是由肺内过敏原驱动的Th2反应引起的，其特征为间歇性气道阻塞、气道高反应性和气道炎症。已观察到过敏性哮喘与微生物感染之间存在负相关。微生物感染可通过诱导1型细胞因子IL-12和IFN-γ的分泌来预防过敏反应。在本研究中，我们检测了给予细菌脂多糖（一种通过Toll样受体4（TLR4）激活先天免疫细胞的典型细菌产物）是否能抑制哮喘小鼠模型中的早期和晚期过敏反应。我们报告称，给予脂多糖可抑制IgE介导的、肥大细胞依赖性的被动皮肤过敏反应、肺部炎症、气道嗜酸性粒细胞增多、黏液分泌和气道高活性。对哮喘样反应的抑制并非由于Th1偏移，因为在IL-12基因敲除（-/-）或IFN-γ基因敲除（-/-）小鼠中这种抑制作用仍然存在。然而，在TLR4或一氧化氮合酶2缺陷的小鼠中未观察到脂多糖的抑制作用。我们的研究结果首次证明，脂多糖通过触发一氧化氮合酶2活性的TLR4依赖性途径在体内抑制Th2反应。
