IL-17相关信号通路分子先天免疫缺陷在慢性黏膜皮肤念珠菌病中的研究及免疫治疗进展

慢性皮肤黏膜念珠菌病(chronic mucocutaneous candidiasis,CMC)较为少见,其为一组临床综合征,其特点为慢性复发性、常规抗真菌治疗难以治愈的皮肤、甲及黏膜的念珠菌感染,主要病原菌为白念珠菌。CMC主要为原发性免疫缺陷性疾病,目前分为两大类,最常见的为CMCD(CMC disease,CMCD),念珠菌感染多局限在皮肤黏膜的表面,不合并系统性白念珠菌感染或其他临床症状;系统性CMC(syndromic chronic mucocutaneous candidiasis,SCMC),除存在CMCD的症状外,可同时伴有其他病原菌的感染或系统性的侵袭性真菌感染或伴有其他临床症状。目前认为无论何种类型的原发性CMC均与细胞因子IL-17相关的信号通路分子基因突变致免疫缺陷相关。信号通路某些分子缺陷导致了Th17的增殖分化受阻、IL-17或者IL-22细胞因子分泌减少,或者中和IL-17、IL-22抗体增多等,由此导致了机体对念珠菌或者其他病原菌的易感性增加。在CMC治疗方面,除了应用传统的抗真菌药物如唑类、多烯类及棘白菌素类药物治疗外,生物制剂或者靶基因治疗都提供了可能的新的治疗策略。本文综述了与IL-17信号通路分子先天性免疫缺陷与CMC的相关性研究,并综述了可能的治疗方法和新的治疗靶点。

Progress in mechanisms and immunological treatment of chronic mucocutaneous candidiasis associated with congenital IL-17 pathway deficiency

Chronic mucocutaneous candidiasis(CMC)is a rare,persistent and recurrent infection affecting skin,nails,and oral and genital mucosae.It is mainly caused by Candida albicans and hard to be cured with routine antifungal therapy.Usually,CMC is a primary immunodeficiency disease and can be divided into two categories.The most common one is CMC disease(CMCD),which defined as Candida infection confined to the surface of the skin and mucous membranes and not complicated by systemic Candida albicans infection or other clinical symptoms.The other category is systemic CMC(SCMC)complicated by infections caused by other pathogens,systemic invasive fungal infections,or other clinical symptoms apart from the symptoms of CMCD.It is currently believed that both CMCD and SCMC are related to immunodeficiency caused by gene mutations related to IL-17 signal pathway.The inhibited Th17 proliferation,decreased secretion of IL-17 or IL-22 cytokine,or increased IL-17 or IL-22 neutralizing antibody induced by the mutations promoted the susceptibility to Candida or other pathogens.In the treatment of CMC,in addition to the traditional antifungal drugs such as azoles,polyenes and echinocandins,biological agents and target gene therapy offer potential new therapeutic strategies.This article reviewed the association between congenital immunodeficiency in the IL-17 signaling pathway and CMC,and the possible immunological therapeutic approaches and new therapeutic targets.