Alburquenque Claudio, Amaro José, Fuentes Marisol, Falconer Mary A, Moreno Claudia, Covarrubias Cristian, Pinto Cristian, Rodas Paula I, Bucarey Sergio A, Hermosilla Germán, Magne Fabien, Tapia Cecilia V
Programa de Microbiología y Micología, Instituto de Ciencias Biomédicas, Facultad de Medicina Universidad de Chile. Santiago de Chile.
Escuela de Tecnología Médica, Facultad de Ciencias, Universidad Mayor, Santiago de Chile.
Med Mycol. 2019 Jun 1;57(4):457-467. doi: 10.1093/mmy/myy068.
Candida albicans is commensal yeast that colonizes skin and mucosa; however, it can become an opportunist pathogen by changing from blastoconidia (commensal form) into hypha (pathogenic form). Each form activates a different cytokines response in epithelial cells. Little is known about the commensal role of C. albicans in the innate immunity. This work studied whether stimulation with C. albicans blastoconidia induces protection in keratinocytes and/or in a reconstituted human epithelium (RHE) infected with C. albicans. For this, inactivated C. albicans blastoconidia was used to stimulate keratinocytes and RHE prior to infection with C. albicans. Blastoconidia induced different cytokine expression profiles; in the case of RHE it decreased interleukin (IL)-1β and IL-10 and increased IL-8, tumor necrosis factor α (TNF-α), and interferon γ (IFN-γ). A significant increase in the expression of human β-defensins (HBD) 2 and HBD3 was observed in blastoconidia stimulated keratinocytes and RHE, associated with impaired growth and viability of C. albicans. Additionally, blastoconidia stimulation decreased the expression of virulence factors in C. albicans that are associated with filamentation (EFG1, CPH1 and NRG1), adhesion (ALS5), and invasion (SAP2). Blastoconidia stimulated RHE was significantly less damaged by C. albicans invasion. These results show that the commensal form of C. albicans would exert a protective effect against self-infection.
白色念珠菌是一种定殖于皮肤和黏膜的共生酵母；然而，它可通过从芽生孢子（共生形式）转变为菌丝（致病形式）而成为机会致病菌。每种形式在上皮细胞中激活不同的细胞因子反应。关于白色念珠菌在固有免疫中的共生作用知之甚少。这项研究旨在探讨用白色念珠菌芽生孢子刺激是否能对感染白色念珠菌的角质形成细胞和/或重组人上皮组织（RHE）起到保护作用。为此，在用白色念珠菌感染之前，使用灭活的白色念珠菌芽生孢子刺激角质形成细胞和RHE。芽生孢子诱导了不同的细胞因子表达谱；在RHE中，它降低了白细胞介素（IL）-1β和IL-10的水平，同时增加了IL-8、肿瘤坏死因子α（TNF-α）和干扰素γ（IFN-γ）的水平。在芽生孢子刺激的角质形成细胞和RHE中观察到人类β-防御素（HBD）2和HBD3的表达显著增加，这与白色念珠菌的生长和活力受损有关。此外，芽生孢子刺激降低了白色念珠菌中与丝状化（EFG1、CPH1和NRG1）、黏附（ALS5）和侵袭（SAP2）相关的毒力因子的表达。芽生孢子刺激的RHE受白色念珠菌侵袭的损伤明显较小。这些结果表明，白色念珠菌的共生形式对自身感染具有保护作用。
