Modulating cytokine microenvironment during T cell activation induces protective RSV-specific lung resident memory T cells in early life in mice
Abstract Maternal immunisation against respiratory viruses provides protection in early life, but as antibodies wane, there can be a gap in coverage. This immunity gap might be filled by inducing pathogen-specific lung tissue-resident T cells (TRM). However, the neonatal mouse lung has a different i...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-12-01
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| Series: | npj Viruses |
| Online Access: | https://doi.org/10.1038/s44298-024-00073-x |
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| _version_ | 1841559804651241472 |
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| author | Ziyin Wang Miko Zhong Chubicka Thomas Ekaterina Kinnear Tom Rice Beth Holder Beate Kampmann John S. Tregoning |
| author_facet | Ziyin Wang Miko Zhong Chubicka Thomas Ekaterina Kinnear Tom Rice Beth Holder Beate Kampmann John S. Tregoning |
| author_sort | Ziyin Wang |
| collection | DOAJ |
| description | Abstract Maternal immunisation against respiratory viruses provides protection in early life, but as antibodies wane, there can be a gap in coverage. This immunity gap might be filled by inducing pathogen-specific lung tissue-resident T cells (TRM). However, the neonatal mouse lung has a different inflammatory environment to the adult lung which affects T cell recruitment. We compared the factors affecting viral-specific TRM recruitment in the lungs of adult or neonatal mice. In contrast to adulthood, we demonstrated that RSV or influenza infection in neonatal mice recruited fewer TRM to the lungs. This was associated with reduced lung levels of CCL5 and CXCL10. Co-administration of CCL5 or CXCL10 at the time of primary T cell activation significantly increased RSV-specific TRM in the lung, protecting mice upon reinfection. These chemokine differences were reflected in responses to infection in human cord blood. Here we show a critical role for CCL5 and CXCL10 in the induction of lung TRM and a possible strategy for boosting responses. |
| format | Article |
| id | doaj-art-526a17d6268b49d5be2ad711279136df |
| institution | Kabale University |
| issn | 2948-1767 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Viruses |
| spelling | doaj-art-526a17d6268b49d5be2ad711279136df2025-01-05T12:10:44ZengNature Portfolionpj Viruses2948-17672024-12-012111010.1038/s44298-024-00073-xModulating cytokine microenvironment during T cell activation induces protective RSV-specific lung resident memory T cells in early life in miceZiyin Wang0Miko Zhong1Chubicka Thomas2Ekaterina Kinnear3Tom Rice4Beth Holder5Beate Kampmann6John S. Tregoning7Department of Infectious Disease, Imperial College LondonDepartment of Infectious Disease, Imperial College LondonDepartment of Infectious Disease, Imperial College LondonDepartment of Infectious Disease, Imperial College LondonDepartment of Metabolism, Digestion and Reproduction, Imperial College LondonDepartment of Metabolism, Digestion and Reproduction, Imperial College LondonCentre for Global Health, Charité UniversitatsmedizinDepartment of Infectious Disease, Imperial College LondonAbstract Maternal immunisation against respiratory viruses provides protection in early life, but as antibodies wane, there can be a gap in coverage. This immunity gap might be filled by inducing pathogen-specific lung tissue-resident T cells (TRM). However, the neonatal mouse lung has a different inflammatory environment to the adult lung which affects T cell recruitment. We compared the factors affecting viral-specific TRM recruitment in the lungs of adult or neonatal mice. In contrast to adulthood, we demonstrated that RSV or influenza infection in neonatal mice recruited fewer TRM to the lungs. This was associated with reduced lung levels of CCL5 and CXCL10. Co-administration of CCL5 or CXCL10 at the time of primary T cell activation significantly increased RSV-specific TRM in the lung, protecting mice upon reinfection. These chemokine differences were reflected in responses to infection in human cord blood. Here we show a critical role for CCL5 and CXCL10 in the induction of lung TRM and a possible strategy for boosting responses.https://doi.org/10.1038/s44298-024-00073-x |
| spellingShingle | Ziyin Wang Miko Zhong Chubicka Thomas Ekaterina Kinnear Tom Rice Beth Holder Beate Kampmann John S. Tregoning Modulating cytokine microenvironment during T cell activation induces protective RSV-specific lung resident memory T cells in early life in mice npj Viruses |
| title | Modulating cytokine microenvironment during T cell activation induces protective RSV-specific lung resident memory T cells in early life in mice |
| title_full | Modulating cytokine microenvironment during T cell activation induces protective RSV-specific lung resident memory T cells in early life in mice |
| title_fullStr | Modulating cytokine microenvironment during T cell activation induces protective RSV-specific lung resident memory T cells in early life in mice |
| title_full_unstemmed | Modulating cytokine microenvironment during T cell activation induces protective RSV-specific lung resident memory T cells in early life in mice |
| title_short | Modulating cytokine microenvironment during T cell activation induces protective RSV-specific lung resident memory T cells in early life in mice |
| title_sort | modulating cytokine microenvironment during t cell activation induces protective rsv specific lung resident memory t cells in early life in mice |
| url | https://doi.org/10.1038/s44298-024-00073-x |
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