Virus-specific IgE enhances airway responsiveness on reinfection with respiratory syncytial virus in newborn mice
Virus-specific IgE enhances airway responsiveness on reinfection with respiratory syncytial virus in newborn mice
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DOI：
10.1016/j.jaci.2008.10.012
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发表时间：
2009-01-01
影响因子：
14.2
通讯作者：
Gelfand, Erwin W.
中科院分区：
文献类型：
--
作者：
Dakhama, Azzeddine;Lee, Young-Mok;Gelfand, Erwin W.
工作背景：呼吸道合胞病毒（RSV）特异性IgE是宿主对RSV感染应答的组成部分，但其在随后增强气道反应性改变中的作用尚不清楚目的：明确RSV特异性IgE在增强新生小鼠再感染气道反应性中的作用。记录RSV特异性IgE反应新生儿感染后，IgE的作用进行了测定，并通过评估气道反应性对reinfection.Results：新生儿感染后，野生型（WT）小鼠RSV特异性IgE反应。在再感染时，这些小鼠发展出增强的气道高反应性（AHR）、气道嗜酸性粒细胞增多和粘液分泌过多，并且它们的T细胞细胞因子反应偏向T（H）2表型。这些改变的应答在IL-4（-/-）/IL-13（-/-）小鼠的再感染中均未发生，并且在这些小鼠的新生儿感染后未检测到RSV特异性IgE。Fc ε RI（-/-）小鼠在再感染时没有出现增强的AHR，气道嗜酸性粒细胞增多和粘液产生显著减弱。这些反应可以在用WT肥大细胞重建的缺陷小鼠中恢复。在RSV感染的新生WT小鼠，抗IgE的管理，防止增强AHR和衰减嗜酸性粒细胞增多和粘液分泌过多的再感染，与减少T（H）2细胞因子的生产和增加IFN-γ production.Conclusion：呼吸道合胞病毒特异性IgE增强T（H）2-偏倚的气道反应性的发展最初感染的小鼠作为新生儿再感染。（J Allergy Clin Immunol 2009;123：138-45.）
Background: Respiratory syncytial virus (RSV)-specific IgE is a component of the host response to RSV infection, but its role in the subsequent enhancement of altered airway responsiveness is unknown.Objective: To define the role of RSV-specific IgE in the enhancement of airway responsiveness on reinfection of newborn mice.Methods: Mice were infected as newborns with RSV and were reinfected 5 weeks later. The role of IgE was determined by documenting RSV-specific IgE response after neonatal infection, and by assessing airway responsiveness on reinfection.Results: After neonatal infection, wild-type (WT) mice developed an RSV-specific IgE response. On reinfection, these mice developed enhanced airway hyperresponsiveness (AHR), airway eosinophilia, and mucus hyperproduction, and their T-cell cytokine response was skewed toward a T(H)2 phenotype. None of these altered responses developed on reinfection of IL4(-/-)/IL-13(-/-) mice, and no RSV-specific IgE could be detected after neonatal infection of these mice. Fc epsilon RI(-/-) mice did not develop the enhanced AHR on reinfection, and airway eosinophilia and mucus production were significantly attenuated. These responses could be restored in deficient mice reconstituted with WT mast cells. In RSV-infected newborn WT mice, administration of anti-IgE prevented the enhancement of AHR and attenuated eosinophilia and mucus hyperproduction on reinfection, an effect that was associated with diminished T(H)2 cytokine production and increased IFN-gamma production.Conclusion: Respiratory syncytial virus-specific IgE enhances the development of T(H)2-biased airway responsiveness on reinfection of mice initially infected as newborns. (J Allergy Clin Immunol 2009;123:138-45.)