Glass Kyle A, Longley Sarah J, Bliss Joseph M, Shaw Sunil K
a Department of Pediatrics; Women & Infants Hospital of Rhode Island ; Providence , RI , USA.
Virulence. 2015;6(5):504-14. doi: 10.1080/21505594.2015.1042643.
Candida parapsilosis is a fungal pathogen that is associated with hematogenously disseminated disease in premature neonates, acutely ill or immunocompromised patients. In cell culture, C. parapsilosis cells are actively and avidly endocytosed by endothelial cells via actin polymerization mediated by N-WASP. Here we present evidence that C. parapsilosis that were internalized by endothelial cells remained alive, and avoided being acidified or otherwise damaged via the host cell. Internalized fungal cells reproduced intracellularly and eventually burst out of the host endothelial cell. When neutrophils were added to endothelium and C. parapsilosis, they patrolled the endothelial surface and efficiently killed most adherent fungal cells prior to endocytosis. But after endocytosis by endothelial cells, internalized fungal cells evaded neutrophil killing. Silencing endothelial N-WASP blocked endocytosis of C. parapsilosis and left fungal cells stranded on the cell surface, where they were susceptible to neutrophil killing. These observations suggest that for C. parapsilosis to escape from the bloodstream, fungi may adhere to and be internalized by endothelial cells before being confronted and phagocytosed by a patrolling leukocyte. Once internalized by endothelial cells, C. parapsilosis may safely replicate to cause further rounds of infection. Immunosurveillance of the intravascular lumen by leukocytes crawling on the endothelial surface and rapid killing of adherent yeast may play a major role in controlling C. parapsilosis dissemination and infected endothelial cells may be a significant reservoir for fungal persistence.
近平滑念珠菌是一种真菌病原体，与早产儿、重症或免疫功能低下患者的血行播散性疾病有关。在细胞培养中，近平滑念珠菌细胞通过由N-WASP介导的肌动蛋白聚合作用，被内皮细胞主动且大量地内吞。在此，我们提供证据表明，被内皮细胞内化的近平滑念珠菌仍保持存活，并避免被宿主细胞酸化或受到其他损害。内化的真菌细胞在细胞内繁殖，最终从宿主内皮细胞中破裂而出。当中性粒细胞添加到内皮细胞和平滑念珠菌中时，它们在内皮表面巡逻，并在吞噬作用之前有效地杀死大多数附着的真菌细胞。但是在内皮细胞进行吞噬作用之后，内化的真菌细胞逃避了中性粒细胞的杀伤。沉默内皮细胞的N-WASP可阻止近平滑念珠菌的内吞作用，并使真菌细胞滞留在细胞表面，在那里它们易被中性粒细胞杀伤。这些观察结果表明，对于近平滑念珠菌而言，要从血液中逃脱，真菌可能在内皮细胞粘附并被内化之后，才会遇到巡逻的白细胞并被吞噬。一旦被内皮细胞内化，近平滑念珠菌可能会安全地复制，从而引发进一步的感染。白细胞在内皮表面爬行对血管腔内进行免疫监视以及对附着酵母的快速杀伤，可能在控制近平滑念珠菌的播散中起主要作用，而被感染的内皮细胞可能是真菌持续存在的重要储存库。
