Induction of regulatory cells by helminth parasites: exploitation for the treatment of inflammatory diseases

被引:135
作者
Finlay, Conor M. [1 ]
Walsh, Kevin P. [1 ]
Mills, Kingston H. G. [1 ]
机构
[1] Univ Dublin Trinity Coll, Trinity Biomed Sci Inst, Sch Biochem & Immunol, Immune Regulat Res Grp, Dublin 2, Ireland
基金
爱尔兰科学基金会;
关键词
Th1/Th2/Th17; cells; regulatory T cells; helminths; hygiene hypothesis; autoimmunity; immune regulation; allergy; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; ALTERNATIVELY ACTIVATED MACROPHAGES; INNATE LYMPHOID-CELLS; GROWTH-FACTOR-BETA; SCHISTOSOMA-MANSONI INFECTION; ALLERGIC AIRWAY INFLAMMATION; REMITTING MULTIPLE-SCLEROSIS; DEPENDENT DIABETES-MELLITUS; NEGLECTED TROPICAL DISEASES; TRICHURIS-SUIS THERAPY;
D O I
10.1111/imr.12164
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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-beta. 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.
引用
收藏
页码:206 / 230
页数:25
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