Emerging Fungal Pathogen Candida auris Evades Neutrophil Attack.
Emerging Fungal Pathogen Candida auris Evades Neutrophil Attack.
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DOI：
10.1128/mbio.01403-18
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发表时间：
2018-08-21
期刊：
影响因子：
6.4
通讯作者：
Nett JE
中科院分区：
文献类型：
--
作者：
Johnson CJ;Davis JM;Huttenlocher A;Kernien JF;Nett JE
耳念珠菌最近成为第一个引起全球公共卫生威胁的真菌病原体。该物种引起医院相关的侵袭性念珠菌病爆发的原因尚不清楚。在这项研究中，我们研究了耳念珠菌与中性粒细胞，白细胞的相互作用，对控制侵袭性真菌感染至关重要。我们表明，人类中性粒细胞不能有效地杀死耳念珠菌。与白色念珠菌相比，嗜中性粒细胞对耳念珠菌的招募较差，并且不能形成嗜中性粒细胞胞外陷阱（NETs），其是具有抗微生物活性的DNA、组蛋白和蛋白质的结构。在混合培养物中，中性粒细胞优先参与并杀死白色念珠菌而不是耳念珠菌。在侵袭性念珠菌病的斑马鱼幼虫模型中对中性粒细胞的成像显示，与白色念珠菌相比，响应于耳念珠菌的中性粒细胞的募集减少约50%。当在斑马鱼后脑中遇到白色念珠菌时，中性粒细胞产生组蛋白云，表明NET的形成。在耳念珠菌感染中未观察到这些结构。中性粒细胞攻击和先天免疫的逃避提供了这种病原体的毒力的解释。新出现的真菌病原体耳念珠菌在世界各地的医院中引起了许多侵袭性疾病的爆发。为什么这个物种导致致命的疾病是未知的。我们的研究结果揭示了中性粒细胞不能杀死耳念珠菌相比，最常见的念珠菌属，白色念珠菌。虽然中性粒细胞在遇到白色念珠菌时产生中性粒细胞胞外陷阱（NET），但这些抗菌结构不会响应耳念珠菌而形成。使用人类中性粒细胞和侵袭性念珠菌病的斑马鱼模型，我们表明，耳念珠菌招募中性粒细胞和逃避免疫攻击。对这种受损的先天免疫反应的鉴定揭示了侵袭性疾病患者的悲惨结局。
Candida auris has recently emerged as the first fungal pathogen to cause a global public health threat. The reason this species is causing hospital-associated outbreaks of invasive candidiasis with high mortality is unknown. In this study, we examine the interaction of C. auris with neutrophils, leukocytes critical for control of invasive fungal infections. We show that human neutrophils do not effectively kill C. auris. Compared to Candida albicans, neutrophils poorly recruited to C. auris and failed to form neutrophil extracellular traps (NETs), which are structures of DNA, histones, and proteins with antimicrobial activity. In mixed cultures, neutrophils preferentially engaged and killed C. albicans over C. auris. Imaging of neutrophils in a zebrafish larval model of invasive candidiasis revealed the recruitment of approximately 50% fewer neutrophils in response to C. auris compared to C. albicans. Upon encounter with C. albicans in the zebrafish hindbrain, neutrophils produced clouds of histones, suggesting the formation of NETs. These structures were not observed in C. auris infection. Evasion of neutrophil attack and innate immunity offers an explanation for the virulence of this pathogen. The emerging fungal pathogen Candida auris has produced numerous outbreaks of invasive disease in hospitals worldwide. Why this species causes deadly disease is unknown. Our findings reveal a failure of neutrophils to kill C. auris compared to the most commonly encountered Candida species, C. albicans. While neutrophils produce neutrophil extracellular traps (NETs) upon encounter with C. albicans, these antimicrobial structures are not formed in response to C. auris. Using human neutrophils and a zebrafish model of invasive candidiasis, we show that C. auris poorly recruits neutrophils and evades immune attack. Identification of this impaired innate immune response to C. auris sheds light on the dismal outcomes for patients with invasive disease.