Neutropenia predisposes patients to life-threatening infection with Candida albicans, a commensal and opportunistic fungal pathogen. How phenotypic variation in C. albicans isolates dictates neutrophil responses is poorly understood. By using a panel of clinical C. albicans strains, here we report that the prototype strain SC5314 induces the most potent accumulation of reactive oxygen species (ROS) and neutrophil extracellular traps (NETs) by human neutrophils of all tested isolates. ROS and NET accumulation positively correlated with the degree of hyphal formation by the isolates, the hypha being the fungal morphotype that promotes pathogenesis. However, there was no correlation of ROS and NET accumulation with fungal killing by neutrophils. Fungal killing was also not correlated with phagocytosis levels or oxidative stress susceptibility of the isolates. The bloodstream isolate P94015 cannot make hyphae and was previously shown to be hyperfit in the murine gut commensalism model. Our results show that P94015 displays poor phagocytosis by neutrophils, the least ROS and NET accumulation of all tested isolates, and resistance to neutrophil-mediated killing. Our data suggest that reduced susceptibility to neutrophils is likely to be independent from a previously described genetic mutation in P94015 that promotes commensalism. Reduced clearance by neutrophils could benefit commensal fitness of C. albicans and could also have promoted the virulence of P94015 in the human patient in the absence of hyphal morphogenesis. Collectively, our study provides new insights into neutrophil interactions with C. albicans and suggests that studying diverse isolates informs knowledge of the relevant aspects of this key immune interaction.

中文翻译：

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白色念珠菌临床分离株的自然变异调节中性粒细胞反应。

中性粒细胞减少症使患者易患白色念珠菌（一种共生和机会性真菌病原体）的危及生命的感染。对白色念珠菌分离株的表型变异如何决定中性粒细胞反应知之甚少。通过使用一组临床白色念珠菌菌株，在这里我们报告原型菌株 SC5314 诱导所有测试分离株的人类中性粒细胞最有效地积累活性氧 (ROS) 和中性粒细胞胞外陷阱 (NET)。ROS 和 NET 积累与分离株形成菌丝的程度呈正相关，菌丝是促进发病的真菌形态。然而，ROS和NET积累与中性粒细胞杀死真菌没有相关性。真菌杀死也与分离物的吞噬水平或氧化应激敏感性无关。血流分离物 P94015 不能产生菌丝，并且先前在鼠肠道共生模型中显示出超拟合。我们的结果表明，P94015 的中性粒细胞吞噬作用较差，所有测试分离株的 ROS 和 NET 积累最少，和抵抗中性粒细胞介导的杀伤。我们的数据表明，对中性粒细胞易感性的降低可能与先前描述的促进共生的 P94015 基因突变无关。中性粒细胞清除率降低可能有利于共生在没有菌丝形态发生的情况下，白色念珠菌也可以促进 P94015 在人类患者中的毒力。总的来说，我们的研究为中性粒细胞与白色念珠菌的相互作用提供了新的见解，并表明研究不同的分离株可以了解这种关键免疫相互作用的相关方面。