IL-17 signalling is critical for controlling subcutaneous adipose tissue dynamics and parasite burden during chronic murine Trypanosoma brucei infection
Abstract In the skin, Trypanosoma brucei colonises the subcutaneous white adipose tissue, and is proposed to be competent for forward transmission. The interaction between parasites, adipose tissue, and the local immune system is likely to drive the adipose tissue wasting and weight loss observed in...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-11-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-42918-8 |
| _version_ | 1797274150873595904 |
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| author | Matthew C. Sinton Praveena R. G. Chandrasegaran Paul Capewell Anneli Cooper Alex Girard John Ogunsola Georgia Perona-Wright Dieudonné M Ngoyi Nono Kuispond Bruno Bucheton Mamadou Camara Shingo Kajimura Cécile Bénézech Neil A. Mabbott Annette MacLeod Juan F. Quintana |
| author_facet | Matthew C. Sinton Praveena R. G. Chandrasegaran Paul Capewell Anneli Cooper Alex Girard John Ogunsola Georgia Perona-Wright Dieudonné M Ngoyi Nono Kuispond Bruno Bucheton Mamadou Camara Shingo Kajimura Cécile Bénézech Neil A. Mabbott Annette MacLeod Juan F. Quintana |
| author_sort | Matthew C. Sinton |
| collection | DOAJ |
| description | Abstract In the skin, Trypanosoma brucei colonises the subcutaneous white adipose tissue, and is proposed to be competent for forward transmission. The interaction between parasites, adipose tissue, and the local immune system is likely to drive the adipose tissue wasting and weight loss observed in cattle and humans infected with T. brucei. However, mechanistically, events leading to subcutaneous white adipose tissue wasting are not fully understood. Here, using several complementary approaches, including mass cytometry by time of flight, bulk and single cell transcriptomics, and in vivo genetic models, we show that T. brucei infection drives local expansion of several IL-17A-producing cells in the murine WAT, including TH17 and Vγ6+ cells. We also show that global IL-17 deficiency, or deletion of the adipocyte IL-17 receptor protect from infection-induced WAT wasting and weight loss. Unexpectedly, we find that abrogation of adipocyte IL-17 signalling results in a significant accumulation of Dpp4 + Pi16 + interstitial preadipocytes and increased extravascular parasites in the WAT, highlighting a critical role for IL-17 signalling in controlling preadipocyte fate, subcutaneous WAT dynamics, and local parasite burden. Taken together, our study highlights the central role of adipocyte IL-17 signalling in controlling WAT responses to infection, suggesting that adipocytes are critical coordinators of tissue dynamics and immune responses to T. brucei infection. |
| first_indexed | 2024-03-07T14:54:16Z |
| format | Article |
| id | doaj.art-34a1cb8324534887a960552c5aa36b6f |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-07T14:54:16Z |
| publishDate | 2023-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-34a1cb8324534887a960552c5aa36b6f2024-03-05T19:30:57ZengNature PortfolioNature Communications2041-17232023-11-0114112110.1038/s41467-023-42918-8IL-17 signalling is critical for controlling subcutaneous adipose tissue dynamics and parasite burden during chronic murine Trypanosoma brucei infectionMatthew C. Sinton0Praveena R. G. Chandrasegaran1Paul Capewell2Anneli Cooper3Alex Girard4John Ogunsola5Georgia Perona-Wright6Dieudonné M Ngoyi7Nono Kuispond8Bruno Bucheton9Mamadou Camara10Shingo Kajimura11Cécile Bénézech12Neil A. Mabbott13Annette MacLeod14Juan F. Quintana15Wellcome Centre for Integrative Parasitology, University of GlasgowWellcome Centre for Integrative Parasitology, University of GlasgowWellcome Centre for Integrative Parasitology, University of GlasgowWellcome Centre for Integrative Parasitology, University of GlasgowWellcome Centre for Integrative Parasitology, University of GlasgowWellcome Centre for Integrative Parasitology, University of GlasgowWellcome Centre for Integrative Parasitology, University of GlasgowDepartment of Parasitology, National Institute of Biomedical ResearchDepartment of Parasitology, National Institute of Biomedical ResearchMember of TrypanoGENMember of TrypanoGENDivision of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical SchoolCentre for Cardiovascular Science, University of EdinburghThe Roslin Institute and Royal (Dick) School of Veterinary Studies, University of EdinburghWellcome Centre for Integrative Parasitology, University of GlasgowWellcome Centre for Integrative Parasitology, University of GlasgowAbstract In the skin, Trypanosoma brucei colonises the subcutaneous white adipose tissue, and is proposed to be competent for forward transmission. The interaction between parasites, adipose tissue, and the local immune system is likely to drive the adipose tissue wasting and weight loss observed in cattle and humans infected with T. brucei. However, mechanistically, events leading to subcutaneous white adipose tissue wasting are not fully understood. Here, using several complementary approaches, including mass cytometry by time of flight, bulk and single cell transcriptomics, and in vivo genetic models, we show that T. brucei infection drives local expansion of several IL-17A-producing cells in the murine WAT, including TH17 and Vγ6+ cells. We also show that global IL-17 deficiency, or deletion of the adipocyte IL-17 receptor protect from infection-induced WAT wasting and weight loss. Unexpectedly, we find that abrogation of adipocyte IL-17 signalling results in a significant accumulation of Dpp4 + Pi16 + interstitial preadipocytes and increased extravascular parasites in the WAT, highlighting a critical role for IL-17 signalling in controlling preadipocyte fate, subcutaneous WAT dynamics, and local parasite burden. Taken together, our study highlights the central role of adipocyte IL-17 signalling in controlling WAT responses to infection, suggesting that adipocytes are critical coordinators of tissue dynamics and immune responses to T. brucei infection.https://doi.org/10.1038/s41467-023-42918-8 |
| spellingShingle | Matthew C. Sinton Praveena R. G. Chandrasegaran Paul Capewell Anneli Cooper Alex Girard John Ogunsola Georgia Perona-Wright Dieudonné M Ngoyi Nono Kuispond Bruno Bucheton Mamadou Camara Shingo Kajimura Cécile Bénézech Neil A. Mabbott Annette MacLeod Juan F. Quintana IL-17 signalling is critical for controlling subcutaneous adipose tissue dynamics and parasite burden during chronic murine Trypanosoma brucei infection Nature Communications |
| title | IL-17 signalling is critical for controlling subcutaneous adipose tissue dynamics and parasite burden during chronic murine Trypanosoma brucei infection |
| title_full | IL-17 signalling is critical for controlling subcutaneous adipose tissue dynamics and parasite burden during chronic murine Trypanosoma brucei infection |
| title_fullStr | IL-17 signalling is critical for controlling subcutaneous adipose tissue dynamics and parasite burden during chronic murine Trypanosoma brucei infection |
| title_full_unstemmed | IL-17 signalling is critical for controlling subcutaneous adipose tissue dynamics and parasite burden during chronic murine Trypanosoma brucei infection |
| title_short | IL-17 signalling is critical for controlling subcutaneous adipose tissue dynamics and parasite burden during chronic murine Trypanosoma brucei infection |
| title_sort | il 17 signalling is critical for controlling subcutaneous adipose tissue dynamics and parasite burden during chronic murine trypanosoma brucei infection |
| url | https://doi.org/10.1038/s41467-023-42918-8 |
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