Department of Medicine, University of Wisconsin, Madison, Wisconsin, USA.
Department of Pediatrics, University of Wisconsin, Madison, Wisconsin, USA.
mBio. 2018 Aug 21;9(4):e01403-18. doi: 10.1128/mBio.01403-18.
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 with neutrophils, leukocytes critical for control of invasive fungal infections. We show that human neutrophils do not effectively kill Compared to , neutrophils poorly recruited to 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 over Imaging of neutrophils in a zebrafish larval model of invasive candidiasis revealed the recruitment of approximately 50% fewer neutrophils in response to compared to Upon encounter with in the zebrafish hindbrain, neutrophils produced clouds of histones, suggesting the formation of NETs. These structures were not observed in infection. Evasion of neutrophil attack and innate immunity offers an explanation for the virulence of this pathogen. The emerging fungal pathogen 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 compared to the most commonly encountered species, While neutrophils produce neutrophil extracellular traps (NETs) upon encounter with , these antimicrobial structures are not formed in response to Using human neutrophils and a zebrafish model of invasive candidiasis, we show that poorly recruits neutrophils and evades immune attack. Identification of this impaired innate immune response to sheds light on the dismal outcomes for patients with invasive disease.
最近，它已成为首个引发全球公共卫生威胁的真菌病原体。目前尚不清楚为什么这种真菌会导致医院相关性侵袭性念珠菌病爆发，并伴有高死亡率。在这项研究中，我们研究了 与中性粒细胞的相互作用，中性粒细胞对于控制侵袭性真菌感染至关重要。我们发现，人类中性粒细胞不能有效地杀死 。与 相比，中性粒细胞对 招募不足，无法形成具有抗菌活性的中性粒细胞胞外陷阱（NETs）。在混合培养物中，中性粒细胞优先与 结合并杀死 ，而不是 。在侵袭性念珠菌病的斑马鱼幼虫模型中对中性粒细胞进行成像，结果显示与 相比， 对 响应时，中性粒细胞的募集量减少了约 50%。当 遇到斑马鱼后脑时，中性粒细胞产生了大量组蛋白，表明形成了 NETs。在 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为该病原体的毒力提供了一种解释。这种新兴的真菌病原体 已在全球医院中引发了多次侵袭性疾病的爆发。为什么这种真菌会导致致命的疾病尚不清楚。我们的研究结果揭示了中性粒细胞无法杀死 的情况，而这种情况与最常见的 物种 相比有所不同。虽然中性粒细胞在遇到 时会产生中性粒细胞胞外陷阱（NETs），但这些抗微生物结构不会在对 产生反应时形成。使用人中性粒细胞和侵袭性念珠菌病的斑马鱼模型，我们表明 对中性粒细胞的招募能力差，并逃避免疫攻击。对 先天免疫反应受损的识别，揭示了侵袭性疾病患者预后不良的原因。
