Interleukin-17 drives sex-dependent weight loss and changes in feeding behaviour during Trypanosoma brucei infection

African trypanosomes, the causative agents of Human and Animal African trypanosomiasis or sleeping sickness, reside in tissue niches proposed to be important for disease outcome and transmission. Here, we demonstrate that parasites in the inguinal white adipose tissue (iWAT) niche induce sexually dimorphic physiological and immunological responses. Following chronic Trypanosoma brucei infection, male mice experience weight loss, reduced adipose tissue mass and altered tissue function, as well as changes in feeding behaviour, whereas females do not. We identified that interleukin-17 (IL-17), a cytokine that we show is elevated in sleeping sickness patients, orchestrates a sex-specific response to T. brucei infection in experimental infections. Deletion of murine IL-17a/f abolishes infection-associated weight loss, alters feeding behaviour, and limits adipose tissue wasting in male mice only. We propose that these effects might be triggered locally in adipocytes via engagement of IL-17 with its cognate receptor leading to lipolysis and tissue wasting, and/or systemically, via IL-17 signalling in the hypothalamus, potentially suggesting that IL-17 signalling coordinates brain-adipose tissue communication during sleeping sickness. Our findings also suggest a key sex-dependent role for the IL-17 isoforms IL-17A and IL-17F in regulating adipose tissue and energy balance during infection. Altogether, the results presented here open new directions to understand energy balance and brain-adipose tissue communication during chronic infection. Male and female wild type C57BL/6 mice were infected with Trypanosoma brucei brucei Antat1.1E for a period of 25 days. We infected 4 mice per group, and we included 4 naïve males and 4 naïve females. At the end of the infection, mice were perfused, and the inguinal white adipose tissue (iWAT) was dissected and snap frozen on dry ice. RNA was purified from whole iWAT, using a standard a Qiagen RNEasy Kit, with a Trizol step