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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
general
IL-17 signalling is critical for controlling subcutaneous adipose tissue dynamics and parasite burden during chronic murine Trypanosoma brucei infection
Nature Communications, Volume 14, No. 1, Article 7070, Year 2023
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Description
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. © 2023, The Author(s).
Authors & Co-Authors
Sinton, Matthew C.
United Kingdom, Glasgow
University of Glasgow
United Kingdom, Manchester
The University of Manchester
Chandrasegaran, Praveena R.G.
United Kingdom, Glasgow
University of Glasgow
Capewell, Paul
United Kingdom, Glasgow
University of Glasgow
Cooper, Anneli
United Kingdom, Glasgow
University of Glasgow
Ogunsola, John O.
United Kingdom, Glasgow
University of Glasgow
Bucheton, Bruno
France, Paris
Cirad
Camara, Mamadou I.
Guinea, Conakry
Ministère de la Santé
Mabbott, Neil Andrew
United Kingdom, Midlothian
University of Edinburgh, Roslin Institute
MacLeod, Annette
United Kingdom, Glasgow
University of Glasgow
Quintana, Juan F.
United Kingdom, Glasgow
University of Glasgow
United Kingdom, Manchester
The University of Manchester
United Kingdom, Manchester
Health Innovation Manchester
Statistics
Authors: 10
Affiliations: 10
Identifiers
Doi:
10.1038/s41467-023-42918-8
ISSN:
20411723
Research Areas
Genetics And Genomics