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白色念珠菌的菌丝入侵会抑制实验性口腔念珠菌病中人类β-防御素的表达。

Hyphal invasion of Candida albicans inhibits the expression of human beta-defensins in experimental oral candidiasis.

作者信息

Lu Qian, Jayatilake Jayalath A M S, Samaranayake Lakshman P, Jin Lijian

机构信息

Periodontology, Faculty of Dentistry, The University of Hong Kong.

出版信息

J Invest Dermatol. 2006 Sep;126(9):2049-56. doi: 10.1038/sj.jid.5700346. Epub 2006 Jun 1.

Abstract

Oral epithelium reacts to microbial challenges by eliciting a defensive response that includes the production of antimicrobial peptides. This study investigated the expression of human beta-defensins-1, 2, and 3 in reconstituted human oral epithelia during experimental oral infections with six different Candida species, and a wild-type C. albicans isolate and five of its mutants. The expression of defensins was induced after 12 hours infection with the wild-type C. albicans, but this response was not seen for the noninvasive hyphal mutants nor the secreted aspartyl proteinase mutants. Furthermore, defensin expression was not detected after 48 hours in epithelia infected with either C. albicans wild-type isolate or its invasive hyphal and proteinase mutants. Most of the non-albicans Candida were capable of inducing the expression of defensins in epithelia after 24 or 48 hours of infection. These Candida-host interaction patterns suggest that the oral epithelia possess mechanisms for sensing the early invasion of C. albicans through recognition of the presence of hyphae and proteinases of Candida and respond to the insult by producing antimicrobial peptides. This hyphal-invasion-dependent inhibition of defensin expression in oral epithelium that undermines the host surveillance system represents a hitherto undescribed novel pathogenic mechanism of C. albicans.

摘要

口腔上皮细胞通过引发包括抗菌肽产生在内的防御反应来应对微生物挑战。本研究调查了在六种不同念珠菌属物种、一株白色念珠菌野生型菌株及其五个突变体引发的实验性口腔感染期间,人β-防御素-1、2和3在重组人口腔上皮中的表达情况。用白色念珠菌野生型菌株感染12小时后,防御素的表达被诱导,但对于非侵袭性菌丝突变体和分泌天冬氨酸蛋白酶突变体,未观察到这种反应。此外,在用白色念珠菌野生型菌株或其侵袭性菌丝和蛋白酶突变体感染的上皮细胞中,48小时后未检测到防御素表达。大多数非白色念珠菌在感染24或48小时后能够在上皮细胞中诱导防御素的表达。这些念珠菌与宿主的相互作用模式表明,口腔上皮细胞具有通过识别念珠菌的菌丝和蛋白酶的存在来感知白色念珠菌早期侵袭的机制,并通过产生抗菌肽来应对这种侵害。这种依赖菌丝侵袭的口腔上皮防御素表达抑制破坏了宿主监测系统,代表了一种迄今为止未被描述的白色念珠菌新致病机制。

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