Break Timothy J, Jaeger Martin, Solis Norma V, Filler Scott G, Rodriguez Carlos A, Lim Jean K, Lee Chyi-Chia Richard, Sobel Jack D, Netea Mihai G, Lionakis Michail S
Fungal Pathogenesis Unit, Laboratory of Clinical Infectious Disease, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.
Radboud University Medical Center and Radboud Center for Infectious Diseases (RCI), Nijmegen, The Netherlands.
Infect Immun. 2015 Mar;83(3):958-65. doi: 10.1128/IAI.02604-14. Epub 2014 Dec 29.
Candida albicans is part of the normal commensal microbiota of mucosal surfaces in a large percentage of the human population. However, perturbations of the host's immune response or bacterial microbiota have been shown to predispose individuals to the development of opportunistic Candida infections. It was recently discovered that a defect in the chemokine receptor CX3CR1 increases susceptibility of mice and humans to systemic candidiasis. However, whether CX3CR1 confers protection against mucosal C. albicans infection has not been investigated. Using two different mouse models, we found that Cx3cr1 is dispensable for the induction of interleukin 17A (IL-17A), IL-22, and IL-23 in the tongue after infection, as well as for the clearance of mucosal candidiasis from the tongue or lower gastrointestinal (GI) tract colonization. Furthermore, the dysfunctional human CX3CR1 allele CX3CR1-M280 was not associated with development of recurrent vulvovaginal candidiasis (RVVC) in women. Taken together, these data indicate that CX3CR1 is not essential for protection of the host against mucosal candidiasis, underscoring the dependence on different mammalian immune factors for control of mucosal versus systemic Candida infections.
白色念珠菌是很大一部分人群黏膜表面正常共生微生物群的组成部分。然而，宿主免疫反应或细菌微生物群的扰动已被证明会使个体易患机会性念珠菌感染。最近发现，趋化因子受体CX3CR1的缺陷会增加小鼠和人类对系统性念珠菌病的易感性。然而，CX3CR1是否能提供针对黏膜白色念珠菌感染的保护作用尚未得到研究。使用两种不同的小鼠模型，我们发现感染后Cx3cr1对于舌部白细胞介素17A（IL-17A）、IL-22和IL-23的诱导以及从舌部清除黏膜念珠菌病或下胃肠道（GI）定植并非必需。此外，功能失调的人类CX3CR1等位基因CX3CR1-M280与女性复发性外阴阴道念珠菌病（RVVC）的发生无关。综上所述，这些数据表明CX3CR1对于宿主抵抗黏膜念珠菌病并非必不可少，这突出了控制黏膜与系统性念珠菌感染对不同哺乳动物免疫因子的依赖性。
