Dietary effects on the course of visceral leishmaniasis in a mouse model 4020

Abstract Description The demographics of leishmaniasis has changed dramatically in endemic regions of Brazil, concurrent with shifts towards a high-fat high-cholesterol diet (HFHC). With this shift, a novel presentation of cutaneous leishmaniasis due to L. braziliensis has emerged in obese patients, characterized by poorer treatment response with higher recurrence rates in obese individuals (Lago, 2021). A direct link between diet-induced changes in metabolic and immune status and the manifestations of visceral leishmaniasis (VL) has not been established. We hypothesize that diet-induced changes in immunometabolism may affect the progression of VL. We examined the effects of diet in a murine model of VL. BALB/c mice were maintained on HFHC, LP, or control diets for 4 weeks, then either infected or not with L. infantum. Inflammation and parasite loads were evaluated by histology, qPCR, and RNAscope. HFHC diet abrogated parasite loads in the liver and caused exacerbated parasite growth in spleens (P < 0.0001). LP diet developed higher parasite loads in livers (P < 0.0001). Control mice developed granulomas in the livers. HFHC mice failed to develop mature granulomas (P < 0.0001). LP mice had increased numbers of small granulomas in the liver (P < 0.0001). These findings suggested that the basal inflammation of the HFHC diet led to failure to contain the parasite and early dissemination of infection to the spleen. Dietary factors may influence the changing spectrum of VL. Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)