Finlay Conor M, Walsh Kevin P, Mills Kingston H G
Immune Regulation Research Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
Immunol Rev. 2014 May;259(1):206-30. doi: 10.1111/imr.12164.
Helminth parasites are highly successful pathogens, chronically infecting a quarter of the world's population, causing significant morbidity but rarely causing death. Protective immunity and expulsion of helminths is mediated by T-helper 2 (Th2) cells, type 2 (M2) macrophages, type 2 innate lymphoid cells, and eosinophils. Failure to mount these type 2 immune responses can result in immunopathology mediated by Th1 or Th17 cells. Helminths have evolved a wide variety of approaches for immune suppression, especially the generation of regulatory T cells and anti-inflammatory cytokines interleukin-10 and transforming growth factor-β. This is a very effective strategy for subverting protective immune responses to prolong their survival in the host but has the bystander effect of modulating immune responses to unrelated antigens. Epidemiological studies in humans have shown that infection with helminth parasites is associated with a low incidence of allergy/asthma and autoimmunity in developing countries. Experimental studies in mice have demonstrated that regulatory immune responses induced by helminth can suppress Th2 and Th1/Th17 responses that mediate allergy and autoimmunity, respectively. This has provided a rational explanation of the 'hygiene hypothesis' and has also led to the exploitation of helminths or their immunomodulatory products in the development of new immunosuppressive therapies for inflammatory diseases in humans.
蠕虫寄生虫是非常成功的病原体，长期感染着全球四分之一的人口，虽会导致严重发病，但很少致人死亡。对蠕虫的保护性免疫和驱逐是由辅助性T细胞2（Th2）、2型（M2）巨噬细胞、2型固有淋巴细胞和嗜酸性粒细胞介导的。无法产生这些2型免疫反应会导致由Th1或Th17细胞介导的免疫病理学。蠕虫已经进化出多种免疫抑制方法，特别是调节性T细胞以及抗炎细胞因子白细胞介素-10和转化生长因子-β的产生。这是一种非常有效的策略，可颠覆保护性免疫反应以延长其在宿主体内的存活时间，但会产生调节对无关抗原的免疫反应的旁观者效应。对人类的流行病学研究表明，在发展中国家，感染蠕虫寄生虫与过敏/哮喘和自身免疫的低发病率相关。对小鼠的实验研究表明，蠕虫诱导的调节性免疫反应可以分别抑制介导过敏和自身免疫的Th2和Th1/Th17反应。这为“卫生假说”提供了合理的解释，也促使人们在开发针对人类炎症性疾病的新型免疫抑制疗法时利用蠕虫或其免疫调节产物。
