Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, Netherlands.
Global Center of Excellence Immunology, Danone Nutricia Research, Utrecht, Netherlands.
Front Immunol. 2021 Dec 23;12:797376. doi: 10.3389/fimmu.2021.797376. eCollection 2021.
Increased exposure to household air pollution and ambient air pollution has become one of the world's major environmental health threats. In developing and developed countries, environmental cigarette smoke (CS) exposure is one of the main sources of household air pollution (HAP). Moreover, results from different epidemiological and experimental studies indicate that there is a strong association between HAP, specifically CS exposure, and the development of allergic diseases that often persists into later life. Here, we investigated the impact of prenatal and postnatal CS exposure on offspring susceptibility to the development of allergic airway responses by using a preclinical mouse model. Pregnant BALB/c mice were exposed to either CS or air during pregnancy and lactation and in order to induce allergic asthma the offspring were sensitized and challenged with house dust mite (HDM). Decreased lung function parameters, like dynamic compliance and pleural pressure, were observed in PBS-treated offspring born to CS-exposed mothers compared to offspring from air-exposed mothers. Maternal CS exposure significantly increased the HDM-induced airway eosinophilia and neutrophilia in the offspring. Prenatal and postnatal CS exposure increased the frequency of Th2 cells in the lungs of HDM-treated offspring compared to offspring born to air-exposed mothers. Offspring born to CS-exposed mothers showed increased levels of IL-4, IL-5 and IL-13 in bronchoalveolar lavage fluid compared to offspring from air-exposed mothers. Ex-vivo restimulation of lung cells isolated from HDM-treated offspring born to CS-exposed mothers also resulted in increased IL-4 production. Finally, serum immunoglobulins levels of HDM-specific IgE and HDM-specific IgG1 were significantly increased upon a HDM challenge in offspring born to CS-exposed mothers compared to offspring from air-exposed mothers. In summary, our results reveal a biological plausibility for the epidemiological studies indicating that prenatal and postnatal CS exposure increases the susceptibility of offspring to allergic immune responses.
暴露于室内空气污染和环境空气污染增加已成为全球主要的环境健康威胁之一。在发展中国家和发达国家，环境香烟烟雾（CS）暴露是室内空气污染（HAP）的主要来源之一。此外，不同的流行病学和实验研究结果表明，HAP，特别是 CS 暴露，与过敏性疾病的发展之间存在很强的关联，而这种关联往往会持续到以后的生活。在这里，我们使用临床前小鼠模型研究了产前和产后 CS 暴露对后代易患过敏性气道反应的影响。在妊娠和哺乳期，将怀孕的 BALB/c 小鼠暴露于 CS 或空气中，为了诱导过敏性哮喘，使后代对屋尘螨（HDM）致敏和激发。与来自空气暴露母亲的后代相比，来自 CS 暴露母亲的后代用 PBS 处理后，肺功能参数（如动态顺应性和胸膜压力）下降。CS 暴露的母亲对子代的 CS 暴露显著增加了 HDM 诱导的气道嗜酸性粒细胞和中性粒细胞增多。与来自空气暴露母亲的后代相比，产前和产后 CS 暴露增加了 HDM 处理后代肺部 Th2 细胞的频率。来自 CS 暴露母亲的后代的支气管肺泡灌洗液中 IL-4、IL-5 和 IL-13 水平升高。与来自空气暴露母亲的后代相比，CS 暴露母亲的后代的肺部细胞在体外分离后经 HDM 刺激后，IL-4 的产生也增加。最后，与来自空气暴露母亲的后代相比，CS 暴露母亲的后代在 HDM 激发后，HDM 特异性 IgE 和 HDM 特异性 IgG1 的血清免疫球蛋白水平显著升高。总之，我们的结果为流行病学研究表明，产前和产后 CS 暴露增加了后代对过敏性免疫反应的易感性提供了生物学上的合理性。
