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Protection against epithelial damage during Candida albicans infection is mediated by PI3K/Akt and mammalian target of rapamycin signaling.

Moyes DL, Shen C, Murciano C, Runglall M, Richardson JP, Arno M, Aldecoa-Otalora E, Naglik JR - J. Infect. Dis. (2013)

Bottom Line: Using reconstituted oral epithelium, we assessed epithelial gene transcriptional responses to Candida albicans infection by microarray.Transcript profiling demonstrated early upregulation of epithelial genes involved in immune responses.Many of these genes constituted components of signaling pathways, but only NF-κB, MAPK, and PI3K/Akt pathways were functionally activated.

View Article: PubMed Central - PubMed

Affiliation: Department of Oral Immunology, King's College London Dental Institute.

ABSTRACT

Background: The ability of epithelial cells (ECs) to discriminate between commensal and pathogenic microbes is essential for healthy living. Key to these interactions are mucosal epithelial responses to pathogen-induced damage.

Methods: Using reconstituted oral epithelium, we assessed epithelial gene transcriptional responses to Candida albicans infection by microarray. Signal pathway activation was monitored by Western blotting and transcription factor enzyme-linked immunosorbent assay, and the role of these pathways in C. albicans-induced damage protection was determined using chemical inhibitors.

Results: Transcript profiling demonstrated early upregulation of epithelial genes involved in immune responses. Many of these genes constituted components of signaling pathways, but only NF-κB, MAPK, and PI3K/Akt pathways were functionally activated. We demonstrate that PI3K/Akt signaling is independent of NF-κB and MAPK signaling and plays a key role in epithelial immune activation and damage protection via mammalian target of rapamycin (mTOR) activation.

Conclusions: PI3K/Akt/mTOR signaling may play a critical role in protecting epithelial cells from damage during mucosal fungal infections independent of NF-κB or MAPK signaling.

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Related in: MedlinePlus

Pathways (A) and networks (B) enriched in reconstituted human oral epithelium 24 hours after infection with Candida albicans.
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JIT824F2: Pathways (A) and networks (B) enriched in reconstituted human oral epithelium 24 hours after infection with Candida albicans.

Mentions: The responses 24 hours postinfection are more heterogeneous, reflecting the variety of stimuli affecting ECs at this time point. The most enriched MetaCore pathways include those involved in metabolism (Figure 2A), and analysis of enriched MetaCore Process Networks identifies several DNA damage-associated processes (Base Excision Repair-Nucleotide Excision Repair (BER-NER) repair [8.9], DNA Mismatch Repair (MMR) repair [6.3], DBS repair [4.9], and core processes [3.9]) (Figure 2B). Furthermore, there is enrichment of networks involved in cell cycle (DNA production (S phase [4.2]), likely linked with DNA repair processes. Along with enrichment in mitochondrial translation genes (translation in mitochondria [2.1]), these may represent a continuation of earlier apoptotic processes. Other enriched processes suggest changes in intercellular communication (NOTCH signaling [2.1]) and stress responses (response to hypoxia and oxidative stress [2.2]). Together, these data suggest a general response to an invasive, damage-inducing pathogen.Figure 2.


Protection against epithelial damage during Candida albicans infection is mediated by PI3K/Akt and mammalian target of rapamycin signaling.

Moyes DL, Shen C, Murciano C, Runglall M, Richardson JP, Arno M, Aldecoa-Otalora E, Naglik JR - J. Infect. Dis. (2013)

Pathways (A) and networks (B) enriched in reconstituted human oral epithelium 24 hours after infection with Candida albicans.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4017362&req=5

JIT824F2: Pathways (A) and networks (B) enriched in reconstituted human oral epithelium 24 hours after infection with Candida albicans.
Mentions: The responses 24 hours postinfection are more heterogeneous, reflecting the variety of stimuli affecting ECs at this time point. The most enriched MetaCore pathways include those involved in metabolism (Figure 2A), and analysis of enriched MetaCore Process Networks identifies several DNA damage-associated processes (Base Excision Repair-Nucleotide Excision Repair (BER-NER) repair [8.9], DNA Mismatch Repair (MMR) repair [6.3], DBS repair [4.9], and core processes [3.9]) (Figure 2B). Furthermore, there is enrichment of networks involved in cell cycle (DNA production (S phase [4.2]), likely linked with DNA repair processes. Along with enrichment in mitochondrial translation genes (translation in mitochondria [2.1]), these may represent a continuation of earlier apoptotic processes. Other enriched processes suggest changes in intercellular communication (NOTCH signaling [2.1]) and stress responses (response to hypoxia and oxidative stress [2.2]). Together, these data suggest a general response to an invasive, damage-inducing pathogen.Figure 2.

Bottom Line: Using reconstituted oral epithelium, we assessed epithelial gene transcriptional responses to Candida albicans infection by microarray.Transcript profiling demonstrated early upregulation of epithelial genes involved in immune responses.Many of these genes constituted components of signaling pathways, but only NF-κB, MAPK, and PI3K/Akt pathways were functionally activated.

View Article: PubMed Central - PubMed

Affiliation: Department of Oral Immunology, King's College London Dental Institute.

ABSTRACT

Background: The ability of epithelial cells (ECs) to discriminate between commensal and pathogenic microbes is essential for healthy living. Key to these interactions are mucosal epithelial responses to pathogen-induced damage.

Methods: Using reconstituted oral epithelium, we assessed epithelial gene transcriptional responses to Candida albicans infection by microarray. Signal pathway activation was monitored by Western blotting and transcription factor enzyme-linked immunosorbent assay, and the role of these pathways in C. albicans-induced damage protection was determined using chemical inhibitors.

Results: Transcript profiling demonstrated early upregulation of epithelial genes involved in immune responses. Many of these genes constituted components of signaling pathways, but only NF-κB, MAPK, and PI3K/Akt pathways were functionally activated. We demonstrate that PI3K/Akt signaling is independent of NF-κB and MAPK signaling and plays a key role in epithelial immune activation and damage protection via mammalian target of rapamycin (mTOR) activation.

Conclusions: PI3K/Akt/mTOR signaling may play a critical role in protecting epithelial cells from damage during mucosal fungal infections independent of NF-κB or MAPK signaling.

Show MeSH
Related in: MedlinePlus