Mgl2+ cDC2s coordinate fungal allergic airway type 2, but not type 17, inflammation in mice
Abstract Fungal spores are abundant in the environment and a major cause of asthma. Originally characterised as a type 2 inflammatory disease, allergic airway inflammation that underpins asthma can also involve type 17 inflammation, which can exacerbate disease causing failure of treatments tailored...
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55663-3 |
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| author | Peter C. Cook Sheila L. Brown Emma L. Houlder Julio Furlong-Silva Daniel P. Conn Stefano A. P. Colombo Syed Baker Freya R. Svedberg Gareth Howell Margherita Bertuzzi Louis Boon Joanne E. Konkel Christopher R. Thornton Judith E. Allen Andrew S. MacDonald |
| author_facet | Peter C. Cook Sheila L. Brown Emma L. Houlder Julio Furlong-Silva Daniel P. Conn Stefano A. P. Colombo Syed Baker Freya R. Svedberg Gareth Howell Margherita Bertuzzi Louis Boon Joanne E. Konkel Christopher R. Thornton Judith E. Allen Andrew S. MacDonald |
| author_sort | Peter C. Cook |
| collection | DOAJ |
| description | Abstract Fungal spores are abundant in the environment and a major cause of asthma. Originally characterised as a type 2 inflammatory disease, allergic airway inflammation that underpins asthma can also involve type 17 inflammation, which can exacerbate disease causing failure of treatments tailored to inhibit type 2 factors. However, the mechanisms that determine the host response to fungi, which can trigger both type 2 and type 17 inflammation in allergic airway disease, remain unclear. Here we find that CD11c+ DCs and CD4+ T cells are essential for development of both type 2 and type 17 airway inflammation in mice repeatedly exposed to inhaled spores. Single cell RNA-sequencing with further multi-parameter cytometry shows that allergic inflammation dramatically alters the proportion of numerous DC clusters in the lung, but that only two of these (Mgl2+ cDC2s and CCR7+ DCs) migrate to the dLNs. Targeted removal of several DC subsets shows that Mgl2+ cDC2 depletion reduces type 2, but not type 17, fungal allergic airway inflammation. These data highlight distinct DC subsets as potential therapeutic targets for the treatment of pulmonary fungal disease. |
| format | Article |
| id | doaj-art-b5ed62feb6d743ecbbd1402e031c2c54 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-b5ed62feb6d743ecbbd1402e031c2c542025-01-26T12:41:47ZengNature PortfolioNature Communications2041-17232025-01-0116111810.1038/s41467-024-55663-3Mgl2+ cDC2s coordinate fungal allergic airway type 2, but not type 17, inflammation in micePeter C. Cook0Sheila L. Brown1Emma L. Houlder2Julio Furlong-Silva3Daniel P. Conn4Stefano A. P. Colombo5Syed Baker6Freya R. Svedberg7Gareth Howell8Margherita Bertuzzi9Louis Boon10Joanne E. Konkel11Christopher R. Thornton12Judith E. Allen13Andrew S. MacDonald14Medical Research Council Centre for Medical Mycology at the University of Exeter, Department of Biosciences, Faculty of Health and Life SciencesLydia Becker Institute of Immunology and Inflammation, University of ManchesterLydia Becker Institute of Immunology and Inflammation, University of ManchesterMedical Research Council Centre for Medical Mycology at the University of Exeter, Department of Biosciences, Faculty of Health and Life SciencesMedical Research Council Centre for Medical Mycology at the University of Exeter, Department of Biosciences, Faculty of Health and Life SciencesLydia Becker Institute of Immunology and Inflammation, University of ManchesterLydia Becker Institute of Immunology and Inflammation, University of ManchesterLydia Becker Institute of Immunology and Inflammation, University of ManchesterLydia Becker Institute of Immunology and Inflammation, University of ManchesterManchester Fungal Infection Group, University of ManchesterJJP BiologicsLydia Becker Institute of Immunology and Inflammation, University of ManchesterDepartment of Biosciences, Faculty of Health and Life Sciences, University of ExeterLydia Becker Institute of Immunology and Inflammation, University of ManchesterLydia Becker Institute of Immunology and Inflammation, University of ManchesterAbstract Fungal spores are abundant in the environment and a major cause of asthma. Originally characterised as a type 2 inflammatory disease, allergic airway inflammation that underpins asthma can also involve type 17 inflammation, which can exacerbate disease causing failure of treatments tailored to inhibit type 2 factors. However, the mechanisms that determine the host response to fungi, which can trigger both type 2 and type 17 inflammation in allergic airway disease, remain unclear. Here we find that CD11c+ DCs and CD4+ T cells are essential for development of both type 2 and type 17 airway inflammation in mice repeatedly exposed to inhaled spores. Single cell RNA-sequencing with further multi-parameter cytometry shows that allergic inflammation dramatically alters the proportion of numerous DC clusters in the lung, but that only two of these (Mgl2+ cDC2s and CCR7+ DCs) migrate to the dLNs. Targeted removal of several DC subsets shows that Mgl2+ cDC2 depletion reduces type 2, but not type 17, fungal allergic airway inflammation. These data highlight distinct DC subsets as potential therapeutic targets for the treatment of pulmonary fungal disease.https://doi.org/10.1038/s41467-024-55663-3 |
| spellingShingle | Peter C. Cook Sheila L. Brown Emma L. Houlder Julio Furlong-Silva Daniel P. Conn Stefano A. P. Colombo Syed Baker Freya R. Svedberg Gareth Howell Margherita Bertuzzi Louis Boon Joanne E. Konkel Christopher R. Thornton Judith E. Allen Andrew S. MacDonald Mgl2+ cDC2s coordinate fungal allergic airway type 2, but not type 17, inflammation in mice Nature Communications |
| title | Mgl2+ cDC2s coordinate fungal allergic airway type 2, but not type 17, inflammation in mice |
| title_full | Mgl2+ cDC2s coordinate fungal allergic airway type 2, but not type 17, inflammation in mice |
| title_fullStr | Mgl2+ cDC2s coordinate fungal allergic airway type 2, but not type 17, inflammation in mice |
| title_full_unstemmed | Mgl2+ cDC2s coordinate fungal allergic airway type 2, but not type 17, inflammation in mice |
| title_short | Mgl2+ cDC2s coordinate fungal allergic airway type 2, but not type 17, inflammation in mice |
| title_sort | mgl2 cdc2s coordinate fungal allergic airway type 2 but not type 17 inflammation in mice |
| url | https://doi.org/10.1038/s41467-024-55663-3 |
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