Role of autophagy genetic variants for the risk of Candida infections.
Role of autophagy genetic variants for the risk of Candida infections.
复制标题
DOI：
10.1093/mmy/myt035
复制
发表时间：
2014-05
期刊：
影响因子：
2.9
通讯作者：
Netea MG
中科院分区：
文献类型：
--
作者：
Rosentul DC;Plantinga TS;Farcas M;Oosting M;Hamza OJ;Scott WK;Alexander BD;Yang JC;Laird GM;Joosten LA;van der Meer JW;Perfect JR;Kullberg BJ;van der Ven AJ;Johnson MD;Netea MG
白色念珠菌可引起血小板减少和危重患者的念珠菌血症，以及CD4+计数低的HIV阳性患者的口咽念珠菌病。然而，并非所有有风险的患者都会发生念珠菌感染，患者的遗传背景可能在感染易感性中发挥作用。自噬介导病原体清除和炎症调节。本研究的目的是评估ATG16L1和IRGM自噬基因的遗传变异对念珠菌血症和口咽念珠菌病易感性的影响。我们评估了ATG16L1和IRGM基因的遗传变异是否影响非洲和欧洲来源的念珠菌血症患者队列中念珠菌血症的易感性。此外，我们还评估了这些多态性对坦桑尼亚HIV阳性人群口咽念珠菌病易感性的影响。已经进行了功能研究以评估ATG16L1和IRGM遗传变体对体外和体内细胞因子产生的影响。结果表明，ATG16L1变体调节TNFα的产生，但不调节其他细胞因子，而在IRGM多态性存在的情况下没有观察到影响。此外，未发现ATG16L1和IRGM遗传变异体中的SNP与念珠菌血症或口咽念珠菌病的发病率之间存在显著关联。总之，尽管对促炎细胞因子产生的调节有中度影响，但自噬基因ATG16L1和IRGM的遗传变异对粘膜和全身念珠菌感染的易感性影响较小。
Candida albicans can cause candidemia in neutropenic and critically ill patients, and oropharyngeal candidiasis in HIV-positive patients with low CD4+ counts. However, not all patients at risk develop Candida infections, and the genetic background of the patient might play a role in the susceptibility to infection. Autophagy mediates pathogen clearance and modulation of inflammation. The aim of this study was to assess the effect of genetic variation in the ATG16L1 and IRGM autophagy genes on the susceptibility to candidemia and oropharyngeal candidiasis. We assessed whether genetic variation in the ATG16L1 and IRGM genes influences susceptibility to candidemia in a cohort of candidemia patients of both African and European origin. In addition, we assessed the effect of these polymorphisms for the susceptibility to oropharyngeal candidiasis in an HIV-positive cohort from Tanzania. Functional studies have been performed to assess the effect of the ATG16L1 and IRGM genetic variants on cytokine production both in vitro and in vivo. The results indicate that ATG16L1 variants modulate production of TNFα, but not other cytokines, while no effects were seen in the presence of IRGM polymorphisms. In addition, no significant associations between the SNPs in the ATG16L1 and IRGM genetic variants and the incidence of candidemia or oropharyngeal candidiasis were identified. In conclusion, despite moderate effects on the modulation of proinflammatory cytokine production, genetic variation in the autophagy genes ATG16L1 and IRGM has a minor impact on the susceptibility to both mucosal and systemic Candida infections.