Logo image
Back
Obesity-Associated Inflammatory Reprogramming Impairs a Granulomatous Response to Leishmania infantum
Journal article   Peer reviewed

Obesity-Associated Inflammatory Reprogramming Impairs a Granulomatous Response to Leishmania infantum

Natalie C. Jarvis, Grace M. Gutzman, Yani Chen, Bayan Zhanbolat, Karen I. Cyndari and Mary E. Wilson
The American journal of tropical medicine and hygiene
09/08/2026
DOI: 10.4269/ajtmh.26-0170
PMCID: PMC13590954
PMID: 42710481

View Online

Abstract

The demographics of leishmaniasis in Brazil have shifted in recent decades, coinciding with dietary changes and an increase in overweight/obesity. Cutaneous leishmaniasis becomes more treatment refractory in obese individuals, highlighting the impact of obesity on disease outcome. The impact of the overweight/obese state on infection with Leishmania infantum , which causes visceral leishmaniasis (VL), is unclear. We previously showed that an obesity-prone diet restricts L. infantum expansion in the livers of mice, but the immunological basis remained unexplored. Herein, we investigated whether this reflected improved granuloma formation and parasite control or a response to diet-induced hepatic steatosis and inflammation. To evaluate hepatic responses to VL during obesity, mice were maintained on a high-fat, high-cholesterol (HFHC) diet or a control diet before and throughout L. infantum infection. High-fat, high-cholesterol feeding significantly reduced hepatic parasite burdens but increased splenic parasite burdens. Control animals developed well-organized hepatic granulomas before local resolution, whereas HFHC-fed mouse livers developed diffuse inflammation and early fibrosis consistent with steatohepatitis. They completely failed to form mature granulomas. Quantitative analysis confirmed organized granulomas in 100% of infected control mice, whereas HFHC-fed infected mice showed no or else loosely aggregated, immature infiltrates in their livers. Transcriptional profiling revealed a pronounced inflammatory response in naïve HFHC-fed livers that was minimally exacerbated by infection. These data suggest that diet-induced obesity does not prevent an inflammatory response to the parasite. Rather, the obesity diet impairs formation of the tissue-specific granulomatous response that might normally contain L. infantum locally in the liver.

Details

Metrics

2 Record Views
Logo image