Sinton, M. C. et al. (2023) IL-17 signalling is critical for controlling subcutaneous adipose tissue dynamics and parasite burden during chronic murine Trypanosoma brucei infection. Nature Communications, 14, 7070. (doi: 10.1038/s41467-023-42918-8) (PMID:37923768) (PMCID:PMC10624677)
![[img]](https://eprints.gla.ac.uk/style/images/fileicons/text.png) |
Text
308850.pdf - Published Version Available under License Creative Commons Attribution. 6MB |
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.
| Item Type: | Articles |
|---|---|
| Additional Information: | This work was funded in part by a Wellcome Trust Institutional Strategic Support Fund award (316917-01 awarded to MCS), a Society for Endocrinology Early Career Grant (316705/0 awarded to MCS), and a Wellcome Centre for Integrative Parasitology FutureScope grant [174811-23] to MCS. This work was also funded in part by a Wellcome Trust Senior Research Fellowship (209511/Z/17/Z awarded to AML). JFQ is funded by a Sir Henry Wellcome postdoctoral fellowship (221640/Z/20/Z awarded to JFQ). PC is funded by a Wellcome Centre for Integrative Parasitology FutureScope grant to JFQ (104111/Z/14/Z awarded to JQ). GPW is funded by an MRC grant (MR/S009779/1). CB is funded by an MRC grant (MR/W018497/1). NAM is supported by a the BBSRC Institute Strategic Programme (BBS/E/D/20002173 and BB/X010937/1). SK is funded by the National Institute of Diabetes and Digestive and Kidney Diseases (DK97441, DK125281 and DK127575) and the Howard Hughes Medical Institute. |
| Keywords: | Trypanosoma brucei, interleukin 17, TH17 cells, Vγ6+ T cells, adipose tissue, adipocytes, interstitial preadipocytes, weight loss. |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Sinton, Dr Matthew and MacLeod, Professor Annette and Quintana, Dr Juan and Ogunsola, Mr John and Capewell, Dr Paul and Cooper, Dr Anneli and Girard, Dr Alexandre and Chandrasegaran, Miss Praveena and Perona-Wright, Dr Georgia |
| Creator Roles: | Sinton, M.Conceptualization, Methodology, Formal analysis, Writing – original draft, Writing – review and editing, Funding acquisition Quintana, J.Conceptualization, Methodology, Formal analysis, Writing – review and editing, Funding acquisition Chandrasegaran, P.Methodology, Formal analysis, Writing – review and editing Ogunsola, J.Methodology, Formal analysis, Writing – review and editing Cooper, A.Methodology Capewell, P.Methodology, Formal analysis Girard, A.Methodology, Writing – review and editing Perona-Wright, G.Methodology, Writing – review and editing MacLeod, A.Methodology, Writing – review and editing, Funding acquisition |
| Authors: | Sinton, M. C., Chandrasegaran, P. R.G., Capewell, P., Cooper, A., Girard, A., Ogunsola, J., Perona-Wright, G., Ngoyi, D. M., Kuispond, N., Bucheton, B., Camara, M., Kajimura, S., Bénézech, C., Mabbott, N. A., MacLeod, A., and Quintana, J. F. |
| College/School: | College of Medical Veterinary and Life Sciences College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine |
| Journal Name: | Nature Communications |
| Publisher: | Nature Research |
| ISSN: | 2041-1723 |
| ISSN (Online): | 2041-1723 |
| Copyright Holders: | Copyright: © The Author(s) 2023 |
| First Published: | First published in Nature Communications 14: 7070 |
| Publisher Policy: | Reproduced under a Creative Commons licence |
University Staff: Request a correction | Enlighten Editors: Update this record
Funder and Project Information
Funder and Project Information