Host-Derived Leukotriene B4 Is Critical for Resistance against Invasive Pulmonary Aspergillosis
Aspergillus fumigatus is a mold that causes severe pulmonary infections. Our knowledge of how immune competent hosts maintain control of fungal infections while constantly being exposed to fungi is rapidly emerging. It is known that timely neutrophil recruitment to and activation in the lungs is cri...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2017.01984/full |
| _version_ | 1818943911073153024 |
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| author | Alayna K. Caffrey-Carr Alayna K. Caffrey-Carr Kimberly M. Hilmer Caitlin H. Kowalski Kelly M. Shepardson Kelly M. Shepardson Rachel M. Temple Robert A. Cramer Joshua J. Obar |
| author_facet | Alayna K. Caffrey-Carr Alayna K. Caffrey-Carr Kimberly M. Hilmer Caitlin H. Kowalski Kelly M. Shepardson Kelly M. Shepardson Rachel M. Temple Robert A. Cramer Joshua J. Obar |
| author_sort | Alayna K. Caffrey-Carr |
| collection | DOAJ |
| description | Aspergillus fumigatus is a mold that causes severe pulmonary infections. Our knowledge of how immune competent hosts maintain control of fungal infections while constantly being exposed to fungi is rapidly emerging. It is known that timely neutrophil recruitment to and activation in the lungs is critical to the host defense against development of invasive pulmonary aspergillosis, but the inflammatory sequelae necessary remains to be fully defined. Here, we show that 5-Lipoxygenase (5-LO) and Leukotriene B4 (LTB4) are critical for leukocyte recruitment and resistance to pulmonary A. fumigatus challenge in a fungal-strain-dependent manner. 5-LO activity was needed in radiosensitive cells for an optimal anti-fungal response and in vivo LTB4 production was at least partially dependent on myeloid-derived hypoxia inducible factor-1α. Overall, this study reveals a role for host-derived leukotriene synthesis in innate immunity to A. fumigatus. |
| first_indexed | 2024-12-20T07:34:50Z |
| format | Article |
| id | doaj.art-7411fbe98c034d999cb689b440db9e7c |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-20T07:34:50Z |
| publishDate | 2018-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-7411fbe98c034d999cb689b440db9e7c2022-12-21T19:48:18ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-01-01810.3389/fimmu.2017.01984315771Host-Derived Leukotriene B4 Is Critical for Resistance against Invasive Pulmonary AspergillosisAlayna K. Caffrey-Carr0Alayna K. Caffrey-Carr1Kimberly M. Hilmer2Caitlin H. Kowalski3Kelly M. Shepardson4Kelly M. Shepardson5Rachel M. Temple6Robert A. Cramer7Joshua J. Obar8Department of Microbiology and Immunology, Montana State University, Bozeman, MT, United StatesDepartment of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH, United StatesDepartment of Microbiology and Immunology, Montana State University, Bozeman, MT, United StatesDepartment of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH, United StatesDepartment of Microbiology and Immunology, Montana State University, Bozeman, MT, United StatesDepartment of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH, United StatesDepartment of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH, United StatesDepartment of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH, United StatesDepartment of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH, United StatesAspergillus fumigatus is a mold that causes severe pulmonary infections. Our knowledge of how immune competent hosts maintain control of fungal infections while constantly being exposed to fungi is rapidly emerging. It is known that timely neutrophil recruitment to and activation in the lungs is critical to the host defense against development of invasive pulmonary aspergillosis, but the inflammatory sequelae necessary remains to be fully defined. Here, we show that 5-Lipoxygenase (5-LO) and Leukotriene B4 (LTB4) are critical for leukocyte recruitment and resistance to pulmonary A. fumigatus challenge in a fungal-strain-dependent manner. 5-LO activity was needed in radiosensitive cells for an optimal anti-fungal response and in vivo LTB4 production was at least partially dependent on myeloid-derived hypoxia inducible factor-1α. Overall, this study reveals a role for host-derived leukotriene synthesis in innate immunity to A. fumigatus.http://journal.frontiersin.org/article/10.3389/fimmu.2017.01984/fullAspergillus fumigatusleukotrienesleukotriene B4neutrophilseosinophilshypoxia inducible factor-1α |
| spellingShingle | Alayna K. Caffrey-Carr Alayna K. Caffrey-Carr Kimberly M. Hilmer Caitlin H. Kowalski Kelly M. Shepardson Kelly M. Shepardson Rachel M. Temple Robert A. Cramer Joshua J. Obar Host-Derived Leukotriene B4 Is Critical for Resistance against Invasive Pulmonary Aspergillosis Frontiers in Immunology Aspergillus fumigatus leukotrienes leukotriene B4 neutrophils eosinophils hypoxia inducible factor-1α |
| title | Host-Derived Leukotriene B4 Is Critical for Resistance against Invasive Pulmonary Aspergillosis |
| title_full | Host-Derived Leukotriene B4 Is Critical for Resistance against Invasive Pulmonary Aspergillosis |
| title_fullStr | Host-Derived Leukotriene B4 Is Critical for Resistance against Invasive Pulmonary Aspergillosis |
| title_full_unstemmed | Host-Derived Leukotriene B4 Is Critical for Resistance against Invasive Pulmonary Aspergillosis |
| title_short | Host-Derived Leukotriene B4 Is Critical for Resistance against Invasive Pulmonary Aspergillosis |
| title_sort | host derived leukotriene b4 is critical for resistance against invasive pulmonary aspergillosis |
| topic | Aspergillus fumigatus leukotrienes leukotriene B4 neutrophils eosinophils hypoxia inducible factor-1α |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2017.01984/full |
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