IL-17 signalling is critical for controlling subcutaneous adipose tissue wasting and parasite burden during chronic Trypanosoma brucei infection [single-cell RNA-seq]

ABSTRACT: 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 V6+ 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE233312 | GEO | 2023/05/27

REPOSITORIES: GEO