Dectin-1/IL-15 Pathway Affords Protection against Extrapulmonary Aspergillus fumigatus Infection by Regulating Natural Killer Cell Survival
Aspergillus fumigatus is a ubiquitous, yet potentially pathogenic, mold. The immune system employs innate receptors, such as dectin-1, to recognize fungal pathogens, but the immunological networks that afford protection are poorly explored. Here, we investigated the role of dectin-1 in anti-A. fumig...
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| Format: | Article |
| Language: | English |
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Karger Publishers
2023-01-01
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| Series: | Journal of Innate Immunity |
| Subjects: | |
| Online Access: | https://www.karger.com/Article/FullText/527188 |
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| author | Fábio S.Y. Yoshikawa Maki Wakatsuki Kosuke Yoshida Rikio Yabe Shota Torigoe Sho Yamasaki Glen N. Barber Shinobu Saijo |
| author_facet | Fábio S.Y. Yoshikawa Maki Wakatsuki Kosuke Yoshida Rikio Yabe Shota Torigoe Sho Yamasaki Glen N. Barber Shinobu Saijo |
| author_sort | Fábio S.Y. Yoshikawa |
| collection | DOAJ |
| description | Aspergillus fumigatus is a ubiquitous, yet potentially pathogenic, mold. The immune system employs innate receptors, such as dectin-1, to recognize fungal pathogens, but the immunological networks that afford protection are poorly explored. Here, we investigated the role of dectin-1 in anti-A. fumigatus response in an experimental model of acute invasive aspergillosis. Mice lacking dectin-1 presented enhanced signs of inflammation, with increased production of inflammatory cytokines and neutrophil infiltration, quickly succumbing to the infection. Curiously, resistance did not require T/B lymphocytes or IL-17. Instead, the main effector function of dectin-1 was the preservation of the NK cell population in the kidneys by the provision of the cytokine IL-15. While the depletion of NK cells impaired host defense in wild-type mice, IL-15 administration restored antifungal responses in dectin-1-deficient mice. Our results uncover a new effector mechanism for dectin-1 in anti-Aspergillus defense, adding an alternative approach to understand the pathophysiology of this infection. |
| first_indexed | 2024-04-10T09:53:58Z |
| format | Article |
| id | doaj.art-2e3b36324ddf4a6ea10b35e1c386d562 |
| institution | Directory Open Access Journal |
| issn | 1662-811X 1662-8128 |
| language | English |
| last_indexed | 2024-04-10T09:53:58Z |
| publishDate | 2023-01-01 |
| publisher | Karger Publishers |
| record_format | Article |
| series | Journal of Innate Immunity |
| spelling | doaj.art-2e3b36324ddf4a6ea10b35e1c386d5622023-02-16T12:58:35ZengKarger PublishersJournal of Innate Immunity1662-811X1662-81282023-01-0115139741110.1159/000527188527188Dectin-1/IL-15 Pathway Affords Protection against Extrapulmonary Aspergillus fumigatus Infection by Regulating Natural Killer Cell SurvivalFábio S.Y. Yoshikawa0https://orcid.org/0000-0002-6112-7107Maki Wakatsuki1Kosuke Yoshida2Rikio Yabe3Shota Torigoe4Sho Yamasaki5Glen N. Barber6Shinobu Saijo7Division of Molecular Immunology, Medical Mycology Research Center, Chiba University, Chiba, JapanDivision of Molecular Immunology, Medical Mycology Research Center, Chiba University, Chiba, JapanDivision of Molecular Immunology, Medical Mycology Research Center, Chiba University, Chiba, JapanDivision of Molecular Immunology, Medical Mycology Research Center, Chiba University, Chiba, JapanDepartment of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, JapanDivision of Molecular Immunology, Medical Mycology Research Center, Chiba University, Chiba, JapanDepartment of Cell Biology, University of Miami, Miller School of Medicine, Miami, FL, USADivision of Molecular Immunology, Medical Mycology Research Center, Chiba University, Chiba, JapanAspergillus fumigatus is a ubiquitous, yet potentially pathogenic, mold. The immune system employs innate receptors, such as dectin-1, to recognize fungal pathogens, but the immunological networks that afford protection are poorly explored. Here, we investigated the role of dectin-1 in anti-A. fumigatus response in an experimental model of acute invasive aspergillosis. Mice lacking dectin-1 presented enhanced signs of inflammation, with increased production of inflammatory cytokines and neutrophil infiltration, quickly succumbing to the infection. Curiously, resistance did not require T/B lymphocytes or IL-17. Instead, the main effector function of dectin-1 was the preservation of the NK cell population in the kidneys by the provision of the cytokine IL-15. While the depletion of NK cells impaired host defense in wild-type mice, IL-15 administration restored antifungal responses in dectin-1-deficient mice. Our results uncover a new effector mechanism for dectin-1 in anti-Aspergillus defense, adding an alternative approach to understand the pathophysiology of this infection.https://www.karger.com/Article/FullText/527188aspergillus fumigatusdectin-1il-15nk cells |
| spellingShingle | Fábio S.Y. Yoshikawa Maki Wakatsuki Kosuke Yoshida Rikio Yabe Shota Torigoe Sho Yamasaki Glen N. Barber Shinobu Saijo Dectin-1/IL-15 Pathway Affords Protection against Extrapulmonary Aspergillus fumigatus Infection by Regulating Natural Killer Cell Survival Journal of Innate Immunity aspergillus fumigatus dectin-1 il-15 nk cells |
| title | Dectin-1/IL-15 Pathway Affords Protection against Extrapulmonary Aspergillus fumigatus Infection by Regulating Natural Killer Cell Survival |
| title_full | Dectin-1/IL-15 Pathway Affords Protection against Extrapulmonary Aspergillus fumigatus Infection by Regulating Natural Killer Cell Survival |
| title_fullStr | Dectin-1/IL-15 Pathway Affords Protection against Extrapulmonary Aspergillus fumigatus Infection by Regulating Natural Killer Cell Survival |
| title_full_unstemmed | Dectin-1/IL-15 Pathway Affords Protection against Extrapulmonary Aspergillus fumigatus Infection by Regulating Natural Killer Cell Survival |
| title_short | Dectin-1/IL-15 Pathway Affords Protection against Extrapulmonary Aspergillus fumigatus Infection by Regulating Natural Killer Cell Survival |
| title_sort | dectin 1 il 15 pathway affords protection against extrapulmonary aspergillus fumigatus infection by regulating natural killer cell survival |
| topic | aspergillus fumigatus dectin-1 il-15 nk cells |
| url | https://www.karger.com/Article/FullText/527188 |
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