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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Virulence
2015 ; 6
(5
): 504-14
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Protection of Candida parapsilosis from neutrophil killing through
internalization by human endothelial cells
#MMPMID26039751
Glass KA
; Longley SJ
; Bliss JM
; Shaw SK
Virulence
2015[]; 6
(5
): 504-14
PMID26039751
show ga
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.