IL-17 signalling is critical for controlling subcutaneous adipose tissue dynamics and parasite burden during chronic Trypanosoma brucei infection
Authors/Creators
- 1. Wellcome Centre for Integrative Parasitology, University of Glasgow, Glasgow, UK
- 2. School of Infection and Immunity, University of Glasgow, Glasgow, UK
- 3. Department of Parasitology, National Institute of Biomedical Research, Kinshasa, Democratic Republic of Congo
- 4. Institut de Recherche pour le Développement, Unité Mixte de Recherche IRD-CIRAD 177, Campus International de Baillarguet, Montpellier, France.
- 5. Programme National de Lutte contre la Trypanosomiase Humaine Africaine, Ministère de la Santé, Conakry, Guinea
- 6. Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA
- 7. Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, EH16 4TJ, Scotland, UK
Description
In the skin, Trypanosoma brucei colonises the subcutaneous white adipose tissue (WAT) and harbours a pool of parasites competent for forward transmission. The interaction between parasites, adipose tissue, and the local immune system is likely to drive adipose tissue wasting and weight loss observed in cattle and humans infected with T. brucei. However, mechanistically, this process is not fully understood. Here, using several complementary approaches including mass cytometry by time of flight, bulk and single cell transcriptomics, we found that T. brucei infection drives a local expansion of several IL-17A-producing cells in the murine WAT, including TH17 and Vg6+ T cells. We also found that global IL-17 deficiency, or mice lacking IL-17 receptor expression specifically on adipocytes, were protected from infection-induced WAT wasting and weight loss. Unexpectedly, we found that abrogation of IL-17 signalling on adipocytes results in higher burden of extravascular parasites in the WAT. Taken together, our study highlights the central role of IL-17 signalling on adipocytes in controlling WAT responses to infection, suggesting that adipocytes are a critical coordinator of the tissue immune response to T. brucei infection.
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