Center of Allergy and Environment (ZAUM), Technical University of Munich and Helmholtz Center Munich, Munich, Germany.
Front Immunol. 2020 Sep 11;11:2106. doi: 10.3389/fimmu.2020.02106. eCollection 2020.
The same mechanisms that enable host defense against helminths also drive allergic inflammation. This suggests that pathomechanisms of allergic diseases represent evolutionary old responses against helminth parasites and that studying antihelminth immunity may provide insights into pathomechanisms of asthma. However, helminths have developed an intricate array of immunoregulatory mechanisms to modulate type 2 immune mechanisms. This has led to the hypothesis that the lack of helminth infection may contribute to the rise in allergic sensitization in modern societies. Indeed, the anti-inflammatory potential of helminth (worm) parasites and their products in allergy and asthma has been recognized for decades. As helminth infections bring about multiple undesired effects including an increased susceptibility to other infections, intended helminth infection is not a feasible approach to broadly prevent or treat allergic asthma. Thus, the development of new helminth-based biopharmaceutics may represent a safer approach of harnessing type 2-suppressive effects of helminths. However, progress regarding the mechanisms and molecules that are employed by helminths to modulate allergic inflammation has been relatively recent. The scavenging of alarmins and the modulation of lipid mediator pathways and macrophage function by helminth proteins have been identified as important immunoregulatory mechanisms targeting innate immunity in asthma and allergy. In addition, by regulating the activation of dendritic cells and by promoting regulatory T-cell responses, helminth proteins can counterregulate the adaptive T helper 2 cell response that drives allergic inflammation. Despite these insights, important open questions remain to be addressed before helminth molecules can be used for the prevention and treatment of asthma and other allergic diseases.
能够抵御寄生虫的宿主防御机制同样也会引发过敏炎症。这表明,过敏疾病的发病机制代表了针对寄生虫的古老进化反应,研究抗寄生虫免疫可能有助于深入了解哮喘的发病机制。然而,寄生虫已经发展出了一系列复杂的免疫调节机制来调节 2 型免疫机制。这导致了一个假设,即缺乏寄生虫感染可能导致现代社会过敏致敏率的上升。事实上,寄生虫(蠕虫)的抗炎潜力及其在过敏和哮喘中的产物已经被认识了几十年。由于寄生虫感染会带来多种不良影响,包括增加对其他感染的易感性,因此有意进行寄生虫感染并不是一种广泛预防或治疗过敏性哮喘的可行方法。因此,开发新的基于寄生虫的生物制药可能代表了一种利用寄生虫 2 型抑制作用的更安全方法。然而,寄生虫用来调节过敏炎症的机制和分子的研究进展相对较新。寄生虫蛋白清除警报素以及调节脂质介质途径和巨噬细胞功能已被确定为针对哮喘和过敏中的固有免疫的重要免疫调节机制。此外,通过调节树突状细胞的激活并促进调节性 T 细胞反应,寄生虫蛋白可以对抗驱动过敏炎症的适应性 T 辅助 2 细胞反应。尽管有这些见解,但在寄生虫分子可用于预防和治疗哮喘和其他过敏疾病之前,仍有重要的问题需要解决。