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Candida albicans-epithelial interactions: dissecting the roles of active penetration, induced endocytosis and host factors on the infection process.

Wächtler B, Citiulo F, Jablonowski N, Förster S, Dalle F, Schaller M, Wilson D, Hube B - PLoS ONE (2012)

Bottom Line: Here we investigated the contributions of the two invasion routes of C. albicans to epithelial invasion.Using selective cellular inhibition approaches and differential fluorescence microscopy, we demonstrate that induced endocytosis contributes considerably to the early time points of invasion, while active penetration represents the dominant epithelial invasion route.Although induced endocytosis depends mainly on Als3-E-cadherin interactions, we observed E-cadherin independent induced endocytosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology-Hans Knoell Institute Jena (HKI), Jena, Germany.

ABSTRACT
Candida albicans frequently causes superficial infections by invading and damaging epithelial cells, but may also cause systemic infections by penetrating through epithelial barriers. C. albicans is a remarkable pathogen because it can invade epithelial cells via two distinct mechanisms: induced endocytosis, analogous to facultative intracellular enteropathogenic bacteria, and active penetration, similar to plant pathogenic fungi. Here we investigated the contributions of the two invasion routes of C. albicans to epithelial invasion. Using selective cellular inhibition approaches and differential fluorescence microscopy, we demonstrate that induced endocytosis contributes considerably to the early time points of invasion, while active penetration represents the dominant epithelial invasion route. Although induced endocytosis depends mainly on Als3-E-cadherin interactions, we observed E-cadherin independent induced endocytosis. Finally, we provide evidence of a protective role for serum factors in oral infection: human serum strongly inhibited C. albicans adhesion to, invasion and damage of oral epithelial cells.

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Differentialinvasion of TR-146 or HeLa epithelial cells by C. albicans. (A) Oral TR-146 or HeLa epithelial cells were co-incubated with 105C. albicans cells (alive or thimerosal killed – Wt+Thim) for either 1, 2 or 3 h. (B) HeLa epithelial cells were co-incubated with 105 indicated C. albicans strains (alive or thimerosal killed) for 3 h. Following fixation, samples were differentially stained and analyzed by fluorescence microscopy. The experiment was performed at least two times in duplicates. */**, indicates significant difference between cell lines (A) or between mutant and wild type (B) (p<0.05/p<0.01, respectively).
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pone-0036952-g003: Differentialinvasion of TR-146 or HeLa epithelial cells by C. albicans. (A) Oral TR-146 or HeLa epithelial cells were co-incubated with 105C. albicans cells (alive or thimerosal killed – Wt+Thim) for either 1, 2 or 3 h. (B) HeLa epithelial cells were co-incubated with 105 indicated C. albicans strains (alive or thimerosal killed) for 3 h. Following fixation, samples were differentially stained and analyzed by fluorescence microscopy. The experiment was performed at least two times in duplicates. */**, indicates significant difference between cell lines (A) or between mutant and wild type (B) (p<0.05/p<0.01, respectively).

Mentions: We reasoned that if induced endocytosis was exclusively reliant on C. albicans- E–cadherin interactions on epithelial cells, then blocking active penetration should completely block invasion of HeLa cells. Indeed, during the first 2 h, killed hyphae invaded HeLa cells very poorly (Wt+Thim (HeLa), Fig. 3A). However, by 3 h, the number of killed hyphae endocytosed by TR-146 and HeLa cells was comparable. This data suggests the existence of a secondary, E-cadherin-independent endocytic pathway.


Candida albicans-epithelial interactions: dissecting the roles of active penetration, induced endocytosis and host factors on the infection process.

Wächtler B, Citiulo F, Jablonowski N, Förster S, Dalle F, Schaller M, Wilson D, Hube B - PLoS ONE (2012)

Differentialinvasion of TR-146 or HeLa epithelial cells by C. albicans. (A) Oral TR-146 or HeLa epithelial cells were co-incubated with 105C. albicans cells (alive or thimerosal killed – Wt+Thim) for either 1, 2 or 3 h. (B) HeLa epithelial cells were co-incubated with 105 indicated C. albicans strains (alive or thimerosal killed) for 3 h. Following fixation, samples were differentially stained and analyzed by fluorescence microscopy. The experiment was performed at least two times in duplicates. */**, indicates significant difference between cell lines (A) or between mutant and wild type (B) (p<0.05/p<0.01, respectively).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3351431&req=5

pone-0036952-g003: Differentialinvasion of TR-146 or HeLa epithelial cells by C. albicans. (A) Oral TR-146 or HeLa epithelial cells were co-incubated with 105C. albicans cells (alive or thimerosal killed – Wt+Thim) for either 1, 2 or 3 h. (B) HeLa epithelial cells were co-incubated with 105 indicated C. albicans strains (alive or thimerosal killed) for 3 h. Following fixation, samples were differentially stained and analyzed by fluorescence microscopy. The experiment was performed at least two times in duplicates. */**, indicates significant difference between cell lines (A) or between mutant and wild type (B) (p<0.05/p<0.01, respectively).
Mentions: We reasoned that if induced endocytosis was exclusively reliant on C. albicans- E–cadherin interactions on epithelial cells, then blocking active penetration should completely block invasion of HeLa cells. Indeed, during the first 2 h, killed hyphae invaded HeLa cells very poorly (Wt+Thim (HeLa), Fig. 3A). However, by 3 h, the number of killed hyphae endocytosed by TR-146 and HeLa cells was comparable. This data suggests the existence of a secondary, E-cadherin-independent endocytic pathway.

Bottom Line: Here we investigated the contributions of the two invasion routes of C. albicans to epithelial invasion.Using selective cellular inhibition approaches and differential fluorescence microscopy, we demonstrate that induced endocytosis contributes considerably to the early time points of invasion, while active penetration represents the dominant epithelial invasion route.Although induced endocytosis depends mainly on Als3-E-cadherin interactions, we observed E-cadherin independent induced endocytosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology-Hans Knoell Institute Jena (HKI), Jena, Germany.

ABSTRACT
Candida albicans frequently causes superficial infections by invading and damaging epithelial cells, but may also cause systemic infections by penetrating through epithelial barriers. C. albicans is a remarkable pathogen because it can invade epithelial cells via two distinct mechanisms: induced endocytosis, analogous to facultative intracellular enteropathogenic bacteria, and active penetration, similar to plant pathogenic fungi. Here we investigated the contributions of the two invasion routes of C. albicans to epithelial invasion. Using selective cellular inhibition approaches and differential fluorescence microscopy, we demonstrate that induced endocytosis contributes considerably to the early time points of invasion, while active penetration represents the dominant epithelial invasion route. Although induced endocytosis depends mainly on Als3-E-cadherin interactions, we observed E-cadherin independent induced endocytosis. Finally, we provide evidence of a protective role for serum factors in oral infection: human serum strongly inhibited C. albicans adhesion to, invasion and damage of oral epithelial cells.

Show MeSH
Related in: MedlinePlus