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Human Epithelial Cells Discriminate between Commensal and Pathogenic Interactions with Candida albicans.

Rast TJ, Kullas AL, Southern PJ, Davis DA - PLoS ONE (2016)

Bottom Line: The commensal fungus, Candida albicans, can cause life-threatening infections in at risk individuals.However, real time PCR and Western blot analysis using a high dose of various C. albicans strains demonstrated that these dose-dependent responses are associated with ability to promote host cell damage.Our studies support the idea that epithelial cells play a key role in the immune system by monitoring the microbial community at mucosal surfaces and initiating defensive responses when this community is dysfunctional.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, University of Minnesota, Minneapolis, MN, United States of America.

ABSTRACT
The commensal fungus, Candida albicans, can cause life-threatening infections in at risk individuals. C. albicans colonizes mucosal surfaces of most people, adhering to and interacting with epithelial cells. At low concentrations, C. albicans is not pathogenic nor does it cause epithelial cell damage in vitro; at high concentrations, C. albicans causes mucosal infections and kills epithelial cells in vitro. Here we show that while there are quantitative dose-dependent differences in exposed epithelial cell populations, these reflect a fundamental qualitative difference in host cell response to C. albicans. Using transcriptional profiling experiments and real time PCR, we found that wild-type C. albicans induce dose-dependent responses from a FaDu epithelial cell line. However, real time PCR and Western blot analysis using a high dose of various C. albicans strains demonstrated that these dose-dependent responses are associated with ability to promote host cell damage. Our studies support the idea that epithelial cells play a key role in the immune system by monitoring the microbial community at mucosal surfaces and initiating defensive responses when this community is dysfunctional. This places epithelial cells at a pivotal position in the interaction with C. albicans as epithelial cells themselves promote C. albicans stimulated damage.

No MeSH data available.


Related in: MedlinePlus

Growth of C. albicans on epithelial cells.Wild-type, rim101Δ/Δ, and efg1 cph1Δ/Δ strains were co-cultured with FaDu epithelial cell monolayers at 37°C in a 5% CO2 incubator. At the indicated times post-infection cells were photographed.
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pone.0153165.g002: Growth of C. albicans on epithelial cells.Wild-type, rim101Δ/Δ, and efg1 cph1Δ/Δ strains were co-cultured with FaDu epithelial cell monolayers at 37°C in a 5% CO2 incubator. At the indicated times post-infection cells were photographed.

Mentions: We considered that differences in epithelial transcriptional responses to the C. albicans mutants could be due to kinetic differences associated with the interaction between the mutants and epithelial cells and not a fundamental difference in the interaction itself. To control for this, we used real time RT-PCR to compare gene expression changes over 32 hours (compared with the 6 hour snap shot used in the original microarrays). We were also concerned that the differences in the yeast-hyphal morphological transition, which is critical for pathogenesis, would promote distinct host cell responses [25]. We found that wild-type yeast cells germinated hyphae within 1 hour post-infection (Fig 2). The hyphae continued to grow over the epithelial cells and formed a hyphal mat within 8 hours. The rim101Δ/Δ mutant also germinated to form hyphae within 1 hour post-infection. However, unlike wild-type C. albicans, the rim101Δ/Δ mutant hyphae grew more slowly and only began branching by 4 hours post-infection. Eight hours post-infection, the rim101Δ/Δ mutant had not formed a complete mat, likely due to the shorter branching hyphae. The efg1Δ/Δ cph1Δ/Δ mutant grew in the yeast form throughout the 32 hour incubation and unlike the wild-type and rim101Δ/Δ cells, the efg1Δ/Δ cph1Δ/Δ mutant was non-adherent and could be dislodged from the epithelial cells with gentle agitation. Thus, if a host response is due to C. albicans morphology, the rim101Δ/Δ mutant should show a kinetic defect due to the less robust hyphal formation and the same effect should be absent in the efg1Δ/Δ cph1Δ/Δ mutant and S. cerevisiae, which do not form hyphae.


Human Epithelial Cells Discriminate between Commensal and Pathogenic Interactions with Candida albicans.

Rast TJ, Kullas AL, Southern PJ, Davis DA - PLoS ONE (2016)

Growth of C. albicans on epithelial cells.Wild-type, rim101Δ/Δ, and efg1 cph1Δ/Δ strains were co-cultured with FaDu epithelial cell monolayers at 37°C in a 5% CO2 incubator. At the indicated times post-infection cells were photographed.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4835109&req=5

pone.0153165.g002: Growth of C. albicans on epithelial cells.Wild-type, rim101Δ/Δ, and efg1 cph1Δ/Δ strains were co-cultured with FaDu epithelial cell monolayers at 37°C in a 5% CO2 incubator. At the indicated times post-infection cells were photographed.
Mentions: We considered that differences in epithelial transcriptional responses to the C. albicans mutants could be due to kinetic differences associated with the interaction between the mutants and epithelial cells and not a fundamental difference in the interaction itself. To control for this, we used real time RT-PCR to compare gene expression changes over 32 hours (compared with the 6 hour snap shot used in the original microarrays). We were also concerned that the differences in the yeast-hyphal morphological transition, which is critical for pathogenesis, would promote distinct host cell responses [25]. We found that wild-type yeast cells germinated hyphae within 1 hour post-infection (Fig 2). The hyphae continued to grow over the epithelial cells and formed a hyphal mat within 8 hours. The rim101Δ/Δ mutant also germinated to form hyphae within 1 hour post-infection. However, unlike wild-type C. albicans, the rim101Δ/Δ mutant hyphae grew more slowly and only began branching by 4 hours post-infection. Eight hours post-infection, the rim101Δ/Δ mutant had not formed a complete mat, likely due to the shorter branching hyphae. The efg1Δ/Δ cph1Δ/Δ mutant grew in the yeast form throughout the 32 hour incubation and unlike the wild-type and rim101Δ/Δ cells, the efg1Δ/Δ cph1Δ/Δ mutant was non-adherent and could be dislodged from the epithelial cells with gentle agitation. Thus, if a host response is due to C. albicans morphology, the rim101Δ/Δ mutant should show a kinetic defect due to the less robust hyphal formation and the same effect should be absent in the efg1Δ/Δ cph1Δ/Δ mutant and S. cerevisiae, which do not form hyphae.

Bottom Line: The commensal fungus, Candida albicans, can cause life-threatening infections in at risk individuals.However, real time PCR and Western blot analysis using a high dose of various C. albicans strains demonstrated that these dose-dependent responses are associated with ability to promote host cell damage.Our studies support the idea that epithelial cells play a key role in the immune system by monitoring the microbial community at mucosal surfaces and initiating defensive responses when this community is dysfunctional.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, University of Minnesota, Minneapolis, MN, United States of America.

ABSTRACT
The commensal fungus, Candida albicans, can cause life-threatening infections in at risk individuals. C. albicans colonizes mucosal surfaces of most people, adhering to and interacting with epithelial cells. At low concentrations, C. albicans is not pathogenic nor does it cause epithelial cell damage in vitro; at high concentrations, C. albicans causes mucosal infections and kills epithelial cells in vitro. Here we show that while there are quantitative dose-dependent differences in exposed epithelial cell populations, these reflect a fundamental qualitative difference in host cell response to C. albicans. Using transcriptional profiling experiments and real time PCR, we found that wild-type C. albicans induce dose-dependent responses from a FaDu epithelial cell line. However, real time PCR and Western blot analysis using a high dose of various C. albicans strains demonstrated that these dose-dependent responses are associated with ability to promote host cell damage. Our studies support the idea that epithelial cells play a key role in the immune system by monitoring the microbial community at mucosal surfaces and initiating defensive responses when this community is dysfunctional. This places epithelial cells at a pivotal position in the interaction with C. albicans as epithelial cells themselves promote C. albicans stimulated damage.

No MeSH data available.


Related in: MedlinePlus