Centre for Asthma and Respiratory Disease and Hunter Medical Research Institute, University of Newcastle, Newcastle, Australia.
J Allergy Clin Immunol. 2010 Mar;125(3):617-25, 625.e1-625.e6. doi: 10.1016/j.jaci.2009.10.018. Epub 2010 Feb 1.
Asthma typically originates in early-life, and the impact of infection during immunologic maturation is a critical factor in disease pathogenesis. The progression of aberrant T(H)2 cell responses and disease development has been attributed to a lack of infections. However, exposure to specific pathogens such as Chlamydia may alter immunologic programming and predispose to asthma.
To investigate the effects of chlamydial infection at different ages on allergic airways disease in later life.
Neonatal, infant, or adult BALB/c mice were infected and 6 weeks later were sensitized and subsequently challenged with ovalbumin. Hallmark features of allergic airways disease were compared with uninfected allergic and nonallergic controls.
Early-life (neonatal and infant) but not adult chlamydial infection enhanced the development of hallmark features of asthma in ovalbumin-induced allergic airways disease. Notably early-life infection increased mucus-secreting cell numbers, IL-13 expression, and airway hyperresponsiveness. Neonatal infection attenuated eosinophil influx and ovalbumin-specific T(H)2 cytokine release and numbers of activated myeloid dendritic cells (DCs) in lymph nodes. By contrast, infant infection augmented features of allergic inflammation with increased airway eosinophils, T(H)2 cytokine, and DC responses. Both neonatal and infant infection increased systemic DC-induced IL-13 release from CD4(+) T cells. The timing of infection had significant effects on lung structure because neonatal but not infant or adult infection induced increases in alveolar diameter.
Early-life respiratory chlamydial infections modulate immune responses, alter lung function and structure, and enhance the severity of allergic airways disease in later life.
哮喘通常起源于生命早期，免疫成熟过程中感染的影响是疾病发病机制的关键因素。异常 T(H)2 细胞反应和疾病发展的进展归因于缺乏感染。然而，暴露于特定病原体，如衣原体，可能会改变免疫编程并导致哮喘。
研究不同年龄的衣原体感染对生命后期过敏性气道疾病的影响。
新生、婴儿或成年 BALB/c 小鼠被感染，6 周后致敏，随后用卵清蛋白进行挑战。将过敏性气道疾病的标志性特征与未感染的过敏性和非过敏性对照进行比较。
生命早期（新生和婴儿期）而不是成年期的衣原体感染增强了卵清蛋白诱导的过敏性气道疾病中哮喘标志性特征的发展。值得注意的是，早期感染增加了黏液分泌细胞数量、IL-13 表达和气道高反应性。新生感染减弱了嗜酸性粒细胞浸润以及卵清蛋白特异性 T(H)2 细胞因子释放和淋巴结中激活的髓样树突状细胞 (DC)数量。相比之下，婴儿期感染增加了气道嗜酸性粒细胞、T(H)2 细胞因子和 DC 反应的过敏性炎症特征。新生和婴儿期感染均增加了系统 DC 从 CD4(+) T 细胞诱导的 IL-13 释放。感染的时间有显著影响，因为新生感染而不是婴儿或成年感染诱导肺泡直径增加。
生命早期的呼吸道衣原体感染调节免疫反应，改变肺功能和结构，并增强生命后期过敏性气道疾病的严重程度。
