Hypoxia-Inducible Factor-1α in Macrophages, but Not in Neutrophils, Is Important for Host Defense during Klebsiella pneumoniae-Induced Pneumosepsis
Hypoxia-inducible factor- (HIF-) 1α has been implicated in the ability of cells to adapt to alterations in oxygen levels. Bacterial stimuli can induce HIF1α in immune cells, including those of myeloid origin. We here determined the role of myeloid cell HIF1α in the host response during pneumonia and...
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| Format: | Article |
| Language: | English |
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Wiley
2021-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2021/9958281 |
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| author | Natasja A. Otto Liza Pereverzeva Valentine Leopold Ivan Ramirez-Moral Joris J. T. H. Roelofs Jeroen W. J. van Heijst Alex F. de Vos Tom van der Poll |
| author_facet | Natasja A. Otto Liza Pereverzeva Valentine Leopold Ivan Ramirez-Moral Joris J. T. H. Roelofs Jeroen W. J. van Heijst Alex F. de Vos Tom van der Poll |
| author_sort | Natasja A. Otto |
| collection | DOAJ |
| description | Hypoxia-inducible factor- (HIF-) 1α has been implicated in the ability of cells to adapt to alterations in oxygen levels. Bacterial stimuli can induce HIF1α in immune cells, including those of myeloid origin. We here determined the role of myeloid cell HIF1α in the host response during pneumonia and sepsis caused by the common human pathogen Klebsiella pneumoniae. To this end, we generated mice deficient for HIF1α in myeloid cells (LysM-cre × Hif1αfl/fl) or neutrophils (Mrp8-cre × Hif1αfl/fl) and infected these with Klebsiella pneumoniae via the airways. Myeloid, but not neutrophil, HIF1α-deficient mice had increased bacterial loads in the lungs and distant organs after infection as compared to control mice, pointing at a role for HIF1α in macrophages. Myeloid HIF1α-deficient mice did not show increased bacterial growth after intravenous infection, suggesting that their phenotype during pneumonia was mediated by lung macrophages. Alveolar and lung interstitial macrophages from LysM-cre × Hif1αfl/fl mice produced lower amounts of the immune enhancing cytokine tumor necrosis factor upon stimulation with Klebsiella, while their capacity to phagocytose or to produce reactive oxygen species was unaltered. Alveolar macrophages did not upregulate glycolysis in response to lipopolysaccharide, irrespective of HIF1α presence. These data suggest a role for HIF1α expressed in lung macrophages in protective innate immunity during pneumonia caused by a common bacterial pathogen. |
| format | Article |
| id | doaj-art-05ffed2539a84bb6bb8a7619f259c664 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-05ffed2539a84bb6bb8a7619f259c6642025-02-03T07:23:32ZengWileyMediators of Inflammation0962-93511466-18612021-01-01202110.1155/2021/99582819958281Hypoxia-Inducible Factor-1α in Macrophages, but Not in Neutrophils, Is Important for Host Defense during Klebsiella pneumoniae-Induced PneumosepsisNatasja A. Otto0Liza Pereverzeva1Valentine Leopold2Ivan Ramirez-Moral3Joris J. T. H. Roelofs4Jeroen W. J. van Heijst5Alex F. de Vos6Tom van der Poll7Center for Experimental and Molecular Medicine, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, NetherlandsCenter for Experimental and Molecular Medicine, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, NetherlandsCenter for Experimental and Molecular Medicine, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, NetherlandsCenter for Experimental and Molecular Medicine, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, NetherlandsAmsterdam Infection & Immunity Institute, Amsterdam, NetherlandsCenter for Experimental and Molecular Medicine, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, NetherlandsCenter for Experimental and Molecular Medicine, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, NetherlandsCenter for Experimental and Molecular Medicine, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, NetherlandsHypoxia-inducible factor- (HIF-) 1α has been implicated in the ability of cells to adapt to alterations in oxygen levels. Bacterial stimuli can induce HIF1α in immune cells, including those of myeloid origin. We here determined the role of myeloid cell HIF1α in the host response during pneumonia and sepsis caused by the common human pathogen Klebsiella pneumoniae. To this end, we generated mice deficient for HIF1α in myeloid cells (LysM-cre × Hif1αfl/fl) or neutrophils (Mrp8-cre × Hif1αfl/fl) and infected these with Klebsiella pneumoniae via the airways. Myeloid, but not neutrophil, HIF1α-deficient mice had increased bacterial loads in the lungs and distant organs after infection as compared to control mice, pointing at a role for HIF1α in macrophages. Myeloid HIF1α-deficient mice did not show increased bacterial growth after intravenous infection, suggesting that their phenotype during pneumonia was mediated by lung macrophages. Alveolar and lung interstitial macrophages from LysM-cre × Hif1αfl/fl mice produced lower amounts of the immune enhancing cytokine tumor necrosis factor upon stimulation with Klebsiella, while their capacity to phagocytose or to produce reactive oxygen species was unaltered. Alveolar macrophages did not upregulate glycolysis in response to lipopolysaccharide, irrespective of HIF1α presence. These data suggest a role for HIF1α expressed in lung macrophages in protective innate immunity during pneumonia caused by a common bacterial pathogen.http://dx.doi.org/10.1155/2021/9958281 |
| spellingShingle | Natasja A. Otto Liza Pereverzeva Valentine Leopold Ivan Ramirez-Moral Joris J. T. H. Roelofs Jeroen W. J. van Heijst Alex F. de Vos Tom van der Poll Hypoxia-Inducible Factor-1α in Macrophages, but Not in Neutrophils, Is Important for Host Defense during Klebsiella pneumoniae-Induced Pneumosepsis Mediators of Inflammation |
| title | Hypoxia-Inducible Factor-1α in Macrophages, but Not in Neutrophils, Is Important for Host Defense during Klebsiella pneumoniae-Induced Pneumosepsis |
| title_full | Hypoxia-Inducible Factor-1α in Macrophages, but Not in Neutrophils, Is Important for Host Defense during Klebsiella pneumoniae-Induced Pneumosepsis |
| title_fullStr | Hypoxia-Inducible Factor-1α in Macrophages, but Not in Neutrophils, Is Important for Host Defense during Klebsiella pneumoniae-Induced Pneumosepsis |
| title_full_unstemmed | Hypoxia-Inducible Factor-1α in Macrophages, but Not in Neutrophils, Is Important for Host Defense during Klebsiella pneumoniae-Induced Pneumosepsis |
| title_short | Hypoxia-Inducible Factor-1α in Macrophages, but Not in Neutrophils, Is Important for Host Defense during Klebsiella pneumoniae-Induced Pneumosepsis |
| title_sort | hypoxia inducible factor 1α in macrophages but not in neutrophils is important for host defense during klebsiella pneumoniae induced pneumosepsis |
| url | http://dx.doi.org/10.1155/2021/9958281 |
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