Iron and Ferritin Modulate MHC Class I Expression and NK Cell Recognition
The ability of pathogens to sequester iron from their host cells and proteins affects their virulence. Moreover, iron is required for various innate host defense mechanisms as well as for acquired immune responses. Therefore, intracellular iron concentration may influence the interplay between patho...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2019-02-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.00224/full |
| _version_ | 1828380501124055040 |
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| author | Rosa Sottile Rosa Sottile Giorgia Federico Cinzia Garofalo Rossana Tallerico Maria Concetta Faniello Barbara Quaresima Costanza Maria Cristiani Maddalena Di Sanzo Gianni Cuda Valeria Ventura Valeria Ventura Arnika Kathleen Wagner Gianluca Contrò Nicola Perrotti Elio Gulletta Soldano Ferrone Klas Kärre Francesco Saverio Costanzo Francesco Saverio Costanzo Francesca Carlomagno Ennio Carbone Ennio Carbone |
| author_facet | Rosa Sottile Rosa Sottile Giorgia Federico Cinzia Garofalo Rossana Tallerico Maria Concetta Faniello Barbara Quaresima Costanza Maria Cristiani Maddalena Di Sanzo Gianni Cuda Valeria Ventura Valeria Ventura Arnika Kathleen Wagner Gianluca Contrò Nicola Perrotti Elio Gulletta Soldano Ferrone Klas Kärre Francesco Saverio Costanzo Francesco Saverio Costanzo Francesca Carlomagno Ennio Carbone Ennio Carbone |
| author_sort | Rosa Sottile |
| collection | DOAJ |
| description | The ability of pathogens to sequester iron from their host cells and proteins affects their virulence. Moreover, iron is required for various innate host defense mechanisms as well as for acquired immune responses. Therefore, intracellular iron concentration may influence the interplay between pathogens and immune system. Here, we investigated whether changes in iron concentrations and intracellular ferritin heavy chain (FTH) abundance may modulate the expression of Major Histocompatibility Complex molecules (MHC), and susceptibility to Natural Killer (NK) cell cytotoxicity. FTH downregulation, either by shRNA transfection or iron chelation, led to MHC surface reduction in primary cancer cells and macrophages. On the contrary, mouse embryonic fibroblasts (MEFs) from NCOA4 null mice accumulated FTH for ferritinophagy impairment and displayed MHC class I cell surface overexpression. Low iron concentration, but not FTH, interfered with IFN-γ receptor signaling, preventing the increase of MHC-class I molecules on the membrane by obstructing STAT1 phosphorylation and nuclear translocation. Finally, iron depletion and FTH downregulation increased the target susceptibility of both primary cancer cells and macrophages to NK cell recognition. In conclusion, the reduction of iron and FTH may influence the expression of MHC class I molecules leading to NK cells activation. |
| first_indexed | 2024-12-10T03:59:21Z |
| format | Article |
| id | doaj.art-b4f9dadda2e54e4e84b4bc5b419386ae |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-10T03:59:21Z |
| publishDate | 2019-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-b4f9dadda2e54e4e84b4bc5b419386ae2022-12-22T02:03:02ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-02-011010.3389/fimmu.2019.00224418669Iron and Ferritin Modulate MHC Class I Expression and NK Cell RecognitionRosa Sottile0Rosa Sottile1Giorgia Federico2Cinzia Garofalo3Rossana Tallerico4Maria Concetta Faniello5Barbara Quaresima6Costanza Maria Cristiani7Maddalena Di Sanzo8Gianni Cuda9Valeria Ventura10Valeria Ventura11Arnika Kathleen Wagner12Gianluca Contrò13Nicola Perrotti14Elio Gulletta15Soldano Ferrone16Klas Kärre17Francesco Saverio Costanzo18Francesco Saverio Costanzo19Francesca Carlomagno20Ennio Carbone21Ennio Carbone22Tumor Immunology and Immunopathology Laboratory, Department of Experimental and Clinical Medicine, University Magna Graecia of Catanzaro, Catanzaro, ItalyDepartment of Microbiology, Cell and Tumor Biology (MTC), Karolinska Institutet, Stockholm, SwedenDepartment of Molecular Medicine and Medical Biotechnologies Federico II University, Naples, ItalyTumor Immunology and Immunopathology Laboratory, Department of Experimental and Clinical Medicine, University Magna Graecia of Catanzaro, Catanzaro, ItalyTumor Immunology and Immunopathology Laboratory, Department of Experimental and Clinical Medicine, University Magna Graecia of Catanzaro, Catanzaro, ItalyResearch Center of Advanced Biochemistry and Molecular Biology, Department of Experimental and Clinical Medicine, Magna Græcia University of Catanzaro, Catanzaro, ItalyResearch Center of Advanced Biochemistry and Molecular Biology, Department of Experimental and Clinical Medicine, Magna Græcia University of Catanzaro, Catanzaro, ItalyTumor Immunology and Immunopathology Laboratory, Department of Experimental and Clinical Medicine, University Magna Graecia of Catanzaro, Catanzaro, ItalyResearch Center of Advanced Biochemistry and Molecular Biology, Department of Experimental and Clinical Medicine, Magna Græcia University of Catanzaro, Catanzaro, ItalyLaboratory of Proteomics, Research Center of Advanced Biochemistry and Molecular Biology, Department of Experimental and Clinical Medicine, Magna Græcia University of Catanzaro, Catanzaro, ItalyTumor Immunology and Immunopathology Laboratory, Department of Experimental and Clinical Medicine, University Magna Graecia of Catanzaro, Catanzaro, ItalyDivision of Clinical Pathology, Department of Health Sciences, Magna Graecia University, Catanzaro, ItalyDepartment of Microbiology, Cell and Tumor Biology (MTC), Karolinska Institutet, Stockholm, SwedenDepartment of Health Sciences, University of Catanzaro Magna Graecia, Catanzaro, ItalyDepartment of Health Sciences, University of Catanzaro Magna Graecia, Catanzaro, ItalyDivision of Clinical Pathology, Department of Health Sciences, Magna Graecia University, Catanzaro, ItalyDepartment of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United StatesDepartment of Microbiology, Cell and Tumor Biology (MTC), Karolinska Institutet, Stockholm, SwedenResearch Center of Advanced Biochemistry and Molecular Biology, Department of Experimental and Clinical Medicine, Magna Græcia University of Catanzaro, Catanzaro, ItalyCIS for Genomics and Molecular Pathology, Magna Graecia University of Catanzaro, Catanzaro, ItalyDepartment of Molecular Medicine and Medical Biotechnologies Federico II University, Naples, ItalyTumor Immunology and Immunopathology Laboratory, Department of Experimental and Clinical Medicine, University Magna Graecia of Catanzaro, Catanzaro, ItalyDepartment of Microbiology, Cell and Tumor Biology (MTC), Karolinska Institutet, Stockholm, SwedenThe ability of pathogens to sequester iron from their host cells and proteins affects their virulence. Moreover, iron is required for various innate host defense mechanisms as well as for acquired immune responses. Therefore, intracellular iron concentration may influence the interplay between pathogens and immune system. Here, we investigated whether changes in iron concentrations and intracellular ferritin heavy chain (FTH) abundance may modulate the expression of Major Histocompatibility Complex molecules (MHC), and susceptibility to Natural Killer (NK) cell cytotoxicity. FTH downregulation, either by shRNA transfection or iron chelation, led to MHC surface reduction in primary cancer cells and macrophages. On the contrary, mouse embryonic fibroblasts (MEFs) from NCOA4 null mice accumulated FTH for ferritinophagy impairment and displayed MHC class I cell surface overexpression. Low iron concentration, but not FTH, interfered with IFN-γ receptor signaling, preventing the increase of MHC-class I molecules on the membrane by obstructing STAT1 phosphorylation and nuclear translocation. Finally, iron depletion and FTH downregulation increased the target susceptibility of both primary cancer cells and macrophages to NK cell recognition. In conclusion, the reduction of iron and FTH may influence the expression of MHC class I molecules leading to NK cells activation.https://www.frontiersin.org/article/10.3389/fimmu.2019.00224/fullMHC-INK cellsironIFNγSTAT1HLA |
| spellingShingle | Rosa Sottile Rosa Sottile Giorgia Federico Cinzia Garofalo Rossana Tallerico Maria Concetta Faniello Barbara Quaresima Costanza Maria Cristiani Maddalena Di Sanzo Gianni Cuda Valeria Ventura Valeria Ventura Arnika Kathleen Wagner Gianluca Contrò Nicola Perrotti Elio Gulletta Soldano Ferrone Klas Kärre Francesco Saverio Costanzo Francesco Saverio Costanzo Francesca Carlomagno Ennio Carbone Ennio Carbone Iron and Ferritin Modulate MHC Class I Expression and NK Cell Recognition Frontiers in Immunology MHC-I NK cells iron IFNγ STAT1 HLA |
| title | Iron and Ferritin Modulate MHC Class I Expression and NK Cell Recognition |
| title_full | Iron and Ferritin Modulate MHC Class I Expression and NK Cell Recognition |
| title_fullStr | Iron and Ferritin Modulate MHC Class I Expression and NK Cell Recognition |
| title_full_unstemmed | Iron and Ferritin Modulate MHC Class I Expression and NK Cell Recognition |
| title_short | Iron and Ferritin Modulate MHC Class I Expression and NK Cell Recognition |
| title_sort | iron and ferritin modulate mhc class i expression and nk cell recognition |
| topic | MHC-I NK cells iron IFNγ STAT1 HLA |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.00224/full |
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