Candida albicans induces Metabolic Reprogramming in human NK cells and responds to Perforin with a Zinc Depletion Response
As part of the innate immune system, natural killer (NK) cells are directly involved in the response to fungal infections. Perforin has been identified as the major effector molecule acting against many fungal pathogens. While several studies have shown that perforin mediated fungicidal effects can...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2016-05-01
|
| Series: | Frontiers in Microbiology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fmicb.2016.00750/full |
| _version_ | 1818066429099900928 |
|---|---|
| author | Daniela eHellwig Jessica eVoigt Maria eBouzani Jürgen eLöffler Daniela eAlbrecht-Eckardt Michael eWeber Sascha eBrunke Ronny eMartin Oliver eKurzai Oliver eKurzai Kerstin eHünniger |
| author_facet | Daniela eHellwig Jessica eVoigt Maria eBouzani Jürgen eLöffler Daniela eAlbrecht-Eckardt Michael eWeber Sascha eBrunke Ronny eMartin Oliver eKurzai Oliver eKurzai Kerstin eHünniger |
| author_sort | Daniela eHellwig |
| collection | DOAJ |
| description | As part of the innate immune system, natural killer (NK) cells are directly involved in the response to fungal infections. Perforin has been identified as the major effector molecule acting against many fungal pathogens. While several studies have shown that perforin mediated fungicidal effects can contribute to fungal clearance, neither the activation of NK cells by fungal pathogens nor the effects of perforin on fungal cells are well understood. In a dual approach, we have studied the global gene expression pattern of primary and cytokine activated NK cells after co-incubation with C. albicans and the transcriptomic adaptation of C. albicans to perforin exposure. NK cells responded to the fungal pathogen with an up-regulation of genes involved in immune signaling and release of cytokines. Furthermore, we observed a pronounced increase of genes involved in glycolysis and glycolysis inhibitor 2-deoxy-D-glucose impaired C. albicans induced NK cell activation. This strongly indicates that metabolic adaptation is a major part of the NK cell response to C. albicans infections. In the fungal pathogen, perforin induced a strong up-regulation of several fungal genes involved in the zinc depletion response, such as PRA1 and ZRT1. These data suggest that fungal zinc homeostasis is linked to the reaction to perforin secreted by NK cells. However, deletion mutants in PRA1 and ZRT1 did not show altered susceptibility to perforin. |
| first_indexed | 2024-12-10T15:07:38Z |
| format | Article |
| id | doaj.art-6031ed72f55c43f9bc4cff9a071f3193 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-10T15:07:38Z |
| publishDate | 2016-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-6031ed72f55c43f9bc4cff9a071f31932022-12-22T01:44:00ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2016-05-01710.3389/fmicb.2016.00750181380Candida albicans induces Metabolic Reprogramming in human NK cells and responds to Perforin with a Zinc Depletion ResponseDaniela eHellwig0Jessica eVoigt1Maria eBouzani2Jürgen eLöffler3Daniela eAlbrecht-Eckardt4Michael eWeber5Sascha eBrunke6Ronny eMartin7Oliver eKurzai8Oliver eKurzai9Kerstin eHünniger10Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-InstituteLeibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-InstituteUniversity Hopsital WürzburgUniversity Hopsital WürzburgBioControl Jena GmbHLeibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-InstituteLeibniz Institute for Natural Product Research an Infection Biology - Hans-Knöll-InstitutLeibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-InstituteLeibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-InstituteFriedrich-Schiller-UniversityLeibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-InstituteAs part of the innate immune system, natural killer (NK) cells are directly involved in the response to fungal infections. Perforin has been identified as the major effector molecule acting against many fungal pathogens. While several studies have shown that perforin mediated fungicidal effects can contribute to fungal clearance, neither the activation of NK cells by fungal pathogens nor the effects of perforin on fungal cells are well understood. In a dual approach, we have studied the global gene expression pattern of primary and cytokine activated NK cells after co-incubation with C. albicans and the transcriptomic adaptation of C. albicans to perforin exposure. NK cells responded to the fungal pathogen with an up-regulation of genes involved in immune signaling and release of cytokines. Furthermore, we observed a pronounced increase of genes involved in glycolysis and glycolysis inhibitor 2-deoxy-D-glucose impaired C. albicans induced NK cell activation. This strongly indicates that metabolic adaptation is a major part of the NK cell response to C. albicans infections. In the fungal pathogen, perforin induced a strong up-regulation of several fungal genes involved in the zinc depletion response, such as PRA1 and ZRT1. These data suggest that fungal zinc homeostasis is linked to the reaction to perforin secreted by NK cells. However, deletion mutants in PRA1 and ZRT1 did not show altered susceptibility to perforin.http://journal.frontiersin.org/Journal/10.3389/fmicb.2016.00750/fullCandida albicansGlycolysisPerforinZincNK cells |
| spellingShingle | Daniela eHellwig Jessica eVoigt Maria eBouzani Jürgen eLöffler Daniela eAlbrecht-Eckardt Michael eWeber Sascha eBrunke Ronny eMartin Oliver eKurzai Oliver eKurzai Kerstin eHünniger Candida albicans induces Metabolic Reprogramming in human NK cells and responds to Perforin with a Zinc Depletion Response Frontiers in Microbiology Candida albicans Glycolysis Perforin Zinc NK cells |
| title | Candida albicans induces Metabolic Reprogramming in human NK cells and responds to Perforin with a Zinc Depletion Response |
| title_full | Candida albicans induces Metabolic Reprogramming in human NK cells and responds to Perforin with a Zinc Depletion Response |
| title_fullStr | Candida albicans induces Metabolic Reprogramming in human NK cells and responds to Perforin with a Zinc Depletion Response |
| title_full_unstemmed | Candida albicans induces Metabolic Reprogramming in human NK cells and responds to Perforin with a Zinc Depletion Response |
| title_short | Candida albicans induces Metabolic Reprogramming in human NK cells and responds to Perforin with a Zinc Depletion Response |
| title_sort | candida albicans induces metabolic reprogramming in human nk cells and responds to perforin with a zinc depletion response |
| topic | Candida albicans Glycolysis Perforin Zinc NK cells |
| url | http://journal.frontiersin.org/Journal/10.3389/fmicb.2016.00750/full |
| work_keys_str_mv | AT danielaehellwig candidaalbicansinducesmetabolicreprogramminginhumannkcellsandrespondstoperforinwithazincdepletionresponse AT jessicaevoigt candidaalbicansinducesmetabolicreprogramminginhumannkcellsandrespondstoperforinwithazincdepletionresponse AT mariaebouzani candidaalbicansinducesmetabolicreprogramminginhumannkcellsandrespondstoperforinwithazincdepletionresponse AT jurgeneloffler candidaalbicansinducesmetabolicreprogramminginhumannkcellsandrespondstoperforinwithazincdepletionresponse AT danielaealbrechteckardt candidaalbicansinducesmetabolicreprogramminginhumannkcellsandrespondstoperforinwithazincdepletionresponse AT michaeleweber candidaalbicansinducesmetabolicreprogramminginhumannkcellsandrespondstoperforinwithazincdepletionresponse AT saschaebrunke candidaalbicansinducesmetabolicreprogramminginhumannkcellsandrespondstoperforinwithazincdepletionresponse AT ronnyemartin candidaalbicansinducesmetabolicreprogramminginhumannkcellsandrespondstoperforinwithazincdepletionresponse AT oliverekurzai candidaalbicansinducesmetabolicreprogramminginhumannkcellsandrespondstoperforinwithazincdepletionresponse AT oliverekurzai candidaalbicansinducesmetabolicreprogramminginhumannkcellsandrespondstoperforinwithazincdepletionresponse AT kerstinehunniger candidaalbicansinducesmetabolicreprogramminginhumannkcellsandrespondstoperforinwithazincdepletionresponse |