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

Abstract

AbstractPrevious work has demonstrated that Trypanosoma brucei occupy several adipose tissue depots, including the subcutaneous adipose tissue in mice and humans, and due to its proximity to the skin, it is proposed to be an important for transmission. Here, we demonstrate that parasites in the inguinal white adipose tissue (iWAT) niche induce sexually dimorphic responses. During infection, male mice experience reduced adipose tissue mass, altered tissue function, and changes in feeding behaviour, whereas females do not. This tissue impairment correlates with an accumulation of TH17 T cells in the iWAT. Genetic ablation of IL-17A/F abolishes infection-associated weight loss and alters feeding behaviour, limiting tissue wasting in male mice. Importantly, we detected a significant elevation in serum IL-17A in sleeping sickness patients, indicating that IL-17A/F signalling is also conserved in humans. We propose a model whereby IL-17A/F acts locally in adipocytes via engagement with its cognate receptor leading to lipolysis and tissue wasting, and/or systemically, via signalling in the hypothalamus to modulate feeding behaviour. Together, our findings suggest key sex-dependent roles for IL-17A/F in regulating adipose tissue and energy balance, as well as a coordinator of brain-adipose tissue communication during sleeping sickness, opening new directions to understand energy balance during infection.