Proteomic analysis of human umbilical vein endothelial cells incubated with Cryptococcus neoformans var. neoformans

Abstract

Cryptococcus neoformans is a medically important fungus and can infect all the organs of the body. As vascular endothelial cell is an important target for C. neoformans to penetrate any organs, the differential protein expression of human umbilical vascular endothelial cell (HUVEC) after incubating with C. neoformans may be the key to penetration. The proteins of HUVECs incubated with C. neoformans and normal HUVECs were collected and purified. After two-dimensional electrophoresis, the differential protein expression was identified by matrix-assisted laser desorption ⁄ ionisation mass spectrometry. The mRNA levels of some proteins were measured by real-time PCR. Three proteins were found significantly overexpressed in HUVECs incubated with C. neoformans, and nine other proteins were downregulated. The mRNA levels of S100A10 and peroxiredoxin I fluctuated with the protein levels. These results suggested that the expressions of peroxiredoxin I and S100A10 were regulated during the process of invasion of HUVECs by C. neoformans. We hypothesise that these proteins take part in the modifications of HUVEC cytoskeleton and the tolerance to oxidative stress, which may affect the process of invasion by C. neoformans.

Cryptococcus neoformans Promotes Its Transmigration into the Central Nervous System by Inducing Molecular and Cellular Changes in Brain Endothelial Cells

“…This is consistent with the 3-fold increase in the expression of annexin A2 and the ϳ2-fold increase in S100A10, proteins involved in recruiting factors to the cytoskeleton (42). This notion is supported by previous results demonstrating that transmigration of C. neoformans often involves a transcellular process that is dependent on cytoskeleton rearrangement (16,43). Indeed, it has been shown that actin reorganization via the dephosphorylation of cofilin plays a significant role in the migration of cryptococci across the blood-brain barrier, and the downregulation of S100A10 in murine brain endothelial cells inhibited the internalization of cryptococci (16,43).…”

“…This notion is supported by previous results demonstrating that transmigration of C. neoformans often involves a transcellular process that is dependent on cytoskeleton rearrangement (16,43). Indeed, it has been shown that actin reorganization via the dephosphorylation of cofilin plays a significant role in the migration of cryptococci across the blood-brain barrier, and the downregulation of S100A10 in murine brain endothelial cells inhibited the internalization of cryptococci (16,43). Accordingly, we found that S100A10 was upregulated during both attachment and internalization, further suggesting that S100A10 facilitates the migration of C. neoformans across the human brain endothelium.…”

Modifications to the composition of the hyphal outer layer of Aspergillus fumigatus modulates HUVEC proteins related to inflammatory and stress responses

“…Cofilin-1 was identified in HUVEC monolayers after interaction with C. neoformans [84], and this protein was also identified in the present work, showing a higher abundance level in HUVECs challenged with Δugm1 [28]. Curiously, the proteomics study of the HUVEC response to C. neoformans suggested the modulation of proteins involved in oxidative stress [84], as shown in the present study for A. fumigatus.…”

“…HBMECs [84,85]. It is known that the host cellular actin cytoskeleton undergoes extensive remodeling during pathogen invasion, and some studies have indicated that cofilin phosphorylation plays an important role in actin dynamics [86,87,88].…”

“…It is known that the host cellular actin cytoskeleton undergoes extensive remodeling during pathogen invasion, and some studies have indicated that cofilin phosphorylation plays an important role in actin dynamics [86,87,88]. Cofilin-1 was identified in HUVEC monolayers after interaction with C. neoformans [84], and this protein was also identified in the present work, showing a higher abundance level in HUVECs challenged with Δugm1 [28]. Curiously, the proteomics study of the HUVEC response to C. neoformans suggested the modulation of proteins involved in oxidative stress [84], as shown in the present study for A. fumigatus.…”