Jacquet Alain
Center of Excellence in Vaccine Research and Development, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Front Allergy. 2021 Mar 11;2:662378. doi: 10.3389/falgy.2021.662378. eCollection 2021.
Whereas house dust mite (HDM) allergy results from a dysregulated Th2-biased adaptive immune response, activation of innate immune signaling pathways is a critical prerequisite for the initiation of HDM sensitizations. Such innate sensing is mainly controlled by the airway epithelium and the skin. The resulting release of epithelial-derived proinflammatory cytokines and innate alarmins such as GM-CSF, IL-25, IL-33 and TSLP mediates the activation of ILC2 cells and cDCs to promote Th2-biased inflammation. Significant progress in the elucidation of HDM innate immune activation has been made in the past decade and highlighted key roles of the LPS/TLR4 axis, chitin-dependent pathways together with HDM protease allergens. However, the precise mechanisms by which HDM allergens are sensed by the innate immune system remain largely unknown. Such investigations are made difficult for several reasons. Among these are (1) the natural association of HDM allergens with immunostimulators from the mite exoskeleton as well as from environmental microorganisms/pollutants or endosymbiotic bacteria; (2) the purification of individual HDM allergens from extracts in sufficient amounts and devoid of any microbial and protein impurities; (3) the production of correctly folded recombinant HDM allergens which could display the same biological activity than their natural counterparts; (4) the accessibility to human epithelial samples with cellular heterogeneities and inter-donor variations; (5) the translation of experimental data from mouse models to humans is almost missing. The goal of the present mini-review is to emphasize some important limitations and pitfalls in the elucidation of innate immunostimulatory properties of HDM allergens.
屋尘螨（HDM）过敏是由失调的Th2偏向性适应性免疫反应引起的，而先天免疫信号通路的激活是HDM致敏启动的关键前提。这种先天感知主要由气道上皮和皮肤控制。上皮来源的促炎细胞因子和先天警报素如GM-CSF、IL-25、IL-33和TSLP的释放介导了ILC2细胞和cDC的激活，以促进Th2偏向性炎症。在过去十年中，HDM先天免疫激活的阐明取得了重大进展，突出了LPS/TLR4轴、几丁质依赖性途径以及HDM蛋白酶过敏原的关键作用。然而，先天免疫系统感知HDM过敏原的确切机制在很大程度上仍然未知。由于几个原因，此类研究变得困难。其中包括：（1）HDM过敏原与来自螨外骨骼以及环境微生物/污染物或内共生细菌的免疫刺激剂的天然关联；（2）从提取物中充分纯化单个HDM过敏原，且不含任何微生物和蛋白质杂质；（3）生产能够显示与其天然对应物相同生物活性的正确折叠的重组HDM过敏原；（4）获取具有细胞异质性和供体间差异的人类上皮样本；（5）几乎没有从小鼠模型到人类的实验数据转化。本综述的目的是强调在阐明HDM过敏原的先天免疫刺激特性方面的一些重要局限性和陷阱。
