Division of Immunology, Infection and Inflammation, Glasgow Biomedical Centre, University of Glasgow, Glasgow, UK.
Clin Exp Immunol. 2010 Mar;159(3):256-67. doi: 10.1111/j.1365-2249.2009.04064.x. Epub 2009 Dec 1.
The dramatic recent rise in the incidence of allergic or autoimmune inflammatory diseases in the West has been proposed to reflect the lack of appropriate priming of the immune response by infectious agents such as parasitic worms during childhood. Consistent with this, there is increasing evidence supporting an inverse relationship between worm infection and T helper type 1/17 (Th1/17)-based inflammatory disorders such as rheumatoid arthritis, inflammatory bowel disease, type 1 diabetes and multiple sclerosis. Perhaps more surprisingly, given that such worms often induce strong Th2-type immune responses, there also appears to be an inverse correlation between parasite load and atopy. These findings therefore suggest that the co-evolution of helminths with hosts, which has resulted in the ability of worms to modulate inflammatory responses to promote parasite survival, has also produced the benefit of protecting the host from pathological lesions arising from aggressive proinflammatory responses to infection or, indeed, aberrant inflammatory responses underlying autoimmune and allergic disorders. By focusing upon the properties of the filarial nematode-derived immunomodulatory molecule, ES-62, in this review we shall discuss the potential of exploiting the immunomodulatory products of parasitic worms to identify and develop novel therapeutics for inflammation.
近年来，西方过敏性或自身免疫性炎症性疾病的发病率急剧上升，据推测，这反映了儿童时期寄生虫等感染因子未能适当引发免疫反应。与此一致，越来越多的证据支持蠕虫感染与 Th1/17（Th1/17）为基础的炎症性疾病（如类风湿关节炎、炎症性肠病、1 型糖尿病和多发性硬化症）之间呈反比关系。也许更令人惊讶的是，鉴于这些蠕虫通常会引起强烈的 Th2 型免疫反应，寄生虫负荷与过敏之间似乎也存在反比关系。这些发现表明，寄生虫与宿主的共同进化，使蠕虫能够调节炎症反应以促进寄生虫的生存，也产生了保护宿主免受感染引起的病理性损伤的益处，或者实际上，保护宿主免受自身免疫和过敏疾病潜在的异常炎症反应的益处。在本文中，我们将重点讨论丝虫衍生的免疫调节分子 ES-62 的特性，讨论利用寄生虫的免疫调节产物来鉴定和开发炎症新疗法的潜力。
