Innate immune responses to mycobacteria and the downregulation of atopic responses

被引:34
作者
Rook, Graham A. W. [1 ]
Martinelli, Roberta
Brunet, Laura Rosa
机构
[1] Royal Free & Univ Coll, Windeyer Inst Med Sci, Dept Med Microbiol, 46 Cleveland St, London W1P 6DB, England
关键词
allergic disorders; gene polymorphisms; immunoregulation by mycobacteria; innate immunity; regulatory T cells;
D O I
10.1097/01.all.0000092602.76804.ad
中图分类号
R392 [医学免疫学];
学科分类号
100102 ;
摘要
Purpose of review Exposure to certain environmental microorganisms can promote the induction of T regulatory cells via the innate immune system. This review explores the possibility that reduced exposure to such organisms is leading to increased immunoregulatory disorders in a subset of individuals in whom this regulatory T-cell-inducing pathway is less efficient. We concentrate on mycobacteria and on asthma, because these are well documented. Recent findings The blood cells of the children of farmers, who are partly protected from allergies, express increased levels of messenger RNA encoding CD14 and TLR2, and polymorphisms of CD14 are linked to allergic manifestations in some studies. Polymorphisms of TLR2 (which recognizes mycobacterial components in concert with CD14) are involved in the pattern of response to mycobacteria, and in the type of leprosy that develops. Similarly, polymorphisms of Nramp1, which affect the response to mycobacteria, are linked with the diseases of immunodysregulation that are increasing in parallel with allergic disorders. Moreover, congenic mice bearing different variants of Nrampl differ in their allergic responses. These parallels are suggestive, in view of the observation that a saprophytic environmental mycobacterium is a potent inducer of regulatory T cells, and has shown significant effects in several phase I/II studies in man. Summary The components of the innate immune system that are involved in responses to mycobacteria overlap with those implicated in allergic disorders. Polymorphisms might define the subset of individuals who develop immunoregulatory disorders. Understanding the role of the innate immune system will facilitate the design of clinical trials using microbial products.
引用
收藏
页码:337 / 342
页数:6
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