Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
Int Arch Allergy Immunol. 2012;158(2):120-30. doi: 10.1159/000330896. Epub 2012 Jan 24.
Compounds which activate the innate immune system, such as lipopolysaccharide, are significant components of ambient air, and extremely difficult to remove from the environment. It is currently unclear how prior inhalation of endotoxin affects allergen sensitization. We examined whether lung-specific endotoxin tolerance induction prior to sensitization can modulate the response to allergen.
Endotoxin tolerance was induced by repeated intratracheal exposure to endotoxin. All mice were then sensitized and challenged by direct intratracheal instillation of cockroach allergen.
After allergen sensitization and challenge, endotoxin tolerant mice had significantly decreased airways hyperresponsiveness to methacholine challenge, which was confirmed by invasive lung function tests. Decreased goblet cell hyperplasia and mucus production were also found by histological assessment. Tolerant mice were protected from airway eosinophilia through the mechanism of reduced CCL11 and CCL24. Interestingly, endotoxin tolerant mice had only a modest reduction in cockroach-specific IgE; however, total IgE was significantly reduced.
These data show that induction of endotoxin tolerance prior to sensitization protects against the hallmark features of asthma-like inflammation, and that transient modulation of innate immunity can have long-lasting effects on adaptive responses.
激活先天免疫系统的化合物，如脂多糖，是环境空气中的重要组成部分，极难从环境中去除。目前尚不清楚先前吸入内毒素如何影响过敏原致敏。我们研究了在致敏前是否可以通过肺内特异性内毒素耐受诱导来调节对过敏原的反应。
通过反复气管内暴露于内毒素来诱导内毒素耐受。然后，所有小鼠都通过直接气管内滴注蟑螂过敏原进行致敏和挑战。
在过敏原致敏和挑战后，内毒素耐受小鼠对乙酰甲胆碱挑战的气道高反应性明显降低，这通过侵入性肺功能测试得到证实。通过组织学评估还发现杯状细胞增生和粘液产生减少。耐受小鼠通过减少 CCL11 和 CCL24 来防止气道嗜酸性粒细胞增多。有趣的是，内毒素耐受小鼠仅对蟑螂特异性 IgE 有适度降低；然而，总 IgE 显著降低。
这些数据表明，在致敏前诱导内毒素耐受可预防类似哮喘的炎症的标志性特征，并且先天免疫的短暂调节可以对适应性反应产生持久影响。
