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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

MAP kinase activation stimulated by C. albicans mutants.Total protein was purified from infected or non-infected FaDu epithelial cell monolayers at defined time points. Proteins were separated by SDS-PAGE and western blots probed with anti-phopho-JNK1/2 (A) or anti-phospho-ERK1/2 (B). A cross-reactive background band (arrowhead) was often observed with the anti-phospho-JNK1/2 antibody. Protein loading was normalized by detection of GAPDH (C). Results shown are representative of three independent experiments.
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pone.0153165.g004: MAP kinase activation stimulated by C. albicans mutants.Total protein was purified from infected or non-infected FaDu epithelial cell monolayers at defined time points. Proteins were separated by SDS-PAGE and western blots probed with anti-phopho-JNK1/2 (A) or anti-phospho-ERK1/2 (B). A cross-reactive background band (arrowhead) was often observed with the anti-phospho-JNK1/2 antibody. Protein loading was normalized by detection of GAPDH (C). Results shown are representative of three independent experiments.

Mentions: The JNK1/2 MAP kinases were phosphorylated 3 hours post-infection with wild-type C. albicans (Fig 4A). JNK1/2 phosphorylation was maintained until 7 hours post-infection when phosphorylation was reduced to background levels. JNK1/2 phosphorylation was delayed and only observed 4–6 hours following infection with the rim101Δ/Δ mutant. JNK1/2 phosphorylation was also markedly reduced during infection with the rim101Δ/Δ mutant when compared to infection by wild-type C. albicans. No JNK1/2 phosphorylation was observed when epithelial cells were infected with the efg1Δ/Δ cph1Δ/Δ mutant nor with S. cerevisiae. These results demonstrate that robust JNK1/2 phosphorylation occurs in response to wild-type C. albicans and is reduced or absent in response to less pathogenic strains.


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

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

MAP kinase activation stimulated by C. albicans mutants.Total protein was purified from infected or non-infected FaDu epithelial cell monolayers at defined time points. Proteins were separated by SDS-PAGE and western blots probed with anti-phopho-JNK1/2 (A) or anti-phospho-ERK1/2 (B). A cross-reactive background band (arrowhead) was often observed with the anti-phospho-JNK1/2 antibody. Protein loading was normalized by detection of GAPDH (C). Results shown are representative of three independent experiments.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0153165.g004: MAP kinase activation stimulated by C. albicans mutants.Total protein was purified from infected or non-infected FaDu epithelial cell monolayers at defined time points. Proteins were separated by SDS-PAGE and western blots probed with anti-phopho-JNK1/2 (A) or anti-phospho-ERK1/2 (B). A cross-reactive background band (arrowhead) was often observed with the anti-phospho-JNK1/2 antibody. Protein loading was normalized by detection of GAPDH (C). Results shown are representative of three independent experiments.
Mentions: The JNK1/2 MAP kinases were phosphorylated 3 hours post-infection with wild-type C. albicans (Fig 4A). JNK1/2 phosphorylation was maintained until 7 hours post-infection when phosphorylation was reduced to background levels. JNK1/2 phosphorylation was delayed and only observed 4–6 hours following infection with the rim101Δ/Δ mutant. JNK1/2 phosphorylation was also markedly reduced during infection with the rim101Δ/Δ mutant when compared to infection by wild-type C. albicans. No JNK1/2 phosphorylation was observed when epithelial cells were infected with the efg1Δ/Δ cph1Δ/Δ mutant nor with S. cerevisiae. These results demonstrate that robust JNK1/2 phosphorylation occurs in response to wild-type C. albicans and is reduced or absent in response to less pathogenic strains.

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