IL-17 signalling is critical for controlling subcutaneous adipose tissue dynamics and parasite burden during chronic murine Trypanosoma brucei infection

Matthew C. Sinton, Praveena R. G. Chandrasegaran, Paul Capewell, Anneli Cooper, Alex Girard, John Ogunsola, Georgia Perona-Wright, Dieudonne M Ngoyi, Nono Kuispond, Bruno Bucheton, Mamadou Camara, Shingo Kajimura, Cecile Benezech, Neil Mabbott, Annette MacLeod, Juan F. Quintana

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.
Original languageEnglish
Article number7070
Pages (from-to)1-21
Number of pages21
JournalNature Communications
Volume14
Issue number1
Early online date3 Nov 2023
DOIs
Publication statusPublished - 3 Nov 2023

Keywords / Materials (for Non-textual outputs)

  • Adipose Tissue
  • Adipose Tissue, White
  • Animals
  • Cachexia
  • Cattle
  • Humans
  • Interleukin-17
  • Mice
  • Parasites
  • Subcutaneous Fat
  • Trypanosoma brucei brucei

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