The enhancement or prevention of airway hyperresponsiveness during reinfection with respiratory syncytial virus is critically dependent on the age at first infection and IL-13 production
The enhancement or prevention of airway hyperresponsiveness during reinfection with respiratory syncytial virus is critically dependent on the age at first infection and IL-13 production
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DOI：
10.4049/jimmunol.175.3.1876
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发表时间：
2005-08-01
影响因子：
4.4
通讯作者：
Gelfand, EW
中科院分区：
文献类型：
--
作者：
Dakhama, A;Park, JW;Gelfand, EW
生命早期的呼吸道合胞病毒（RSV）感染被怀疑在毛细支气管炎后喘息和哮喘的发生中起作用。各年龄段再感染都很常见，但决定再感染后气道功能改变的因素尚不十分清楚。本研究在小鼠模型中进行，以明确年龄在确定再感染后对气道功能影响方面的作用。小鼠在出生后不久或断奶时感染，5周后再感染，随后评估气道功能、气道炎症和肺组织病理学。断奶时感染的小鼠在再感染时引发了一种保护性的气道反应。在该年龄组中，再感染导致气道炎症增加，但未出现气道高反应性（AHR）或嗜酸性粒细胞增多，且白细胞介素 - 13（IL - 13）水平降低。相比之下，新生期感染未能保护气道，并在再感染后导致AHR增强。这种二次反应与气道嗜酸性粒细胞增多、IL - 13水平升高和黏液过度产生有关。肺中CD4阳性和CD8阳性的T细胞都是IL - 13的来源，抑制IL - 13可消除这些小鼠的AHR和黏液产生。接种紫外线灭活的病毒未能引发对再感染的这些不同反应，强调了初次接触时肺部主动感染的必要性。因此，新生期RSV感染使再感染时通过一种依赖IL - 13的机制易发生气道嗜酸性粒细胞增多和AHR增强，而较晚年龄的感染可防止再感染后这些气道反应改变的发生。
Respiratory syncytial virus (RSV) infection in early life is suspected to play a role in the development of postbronchiolitis wheezing and asthma. Reinfection is common at all ages, but factors that determine the development of altered airway function after reinfection are not well understood. This study was conducted in a mouse model to define the role of age in determining the consequences on airway function after reinfection. Mice were infected shortly after birth or at weaning and were reinfected 5 wk later, followed by assessment of airway function, airway inflammation, and lung histopathology. Infection of mice at weaning elicited a protective airway response upon reinfection. In this age group, reinfection resulted in increased airway inflammation, but without development of airway hyperresponsiveness (AHR) or eosinophilia and decreased IL-13 levels. By contrast, neonatal infection failed to protect the airways and resulted in enhanced AHR after reinfection. This secondary response was associated with the development of airway eosinophilia, increased IL-13 levels, and mucus hyperproduction. Both CD4- and CD8-positive T cells were a source of IL-13 in the lung, and inhibition of IL-13 abolished AHR and mucus production in these mice. Inoculation of UV-inactivated virus failed to elicit these divergent responses to reinfection, emphasizing the requirement for active lung infection during initial exposure. Thus, neonatal RSV infection predisposes to the development of airway eosinophilia and enhanced AHR via an IL-13-dependent mechanism during reinfection, whereas infection at a later age protects against the development of these altered airway responses after reinfection.