Nutrition, immunometabolism and malaria
Host nutrition can affect the outcome of parasitic diseases through metabolic effects on host immunity and/or the parasite. We study how host nutrition interacts with the host innate and adaptive immune responses to parasitic infection and disease outcome in a rodent model of malaria.
Cerebral malaria (CM) is the most dangerous sequela of Plasmodium falciparum infection resulting in high mortality and morbidity. While little is known about the pathophysiology of cerebral malaria in humans, models of experimental cerebral malaria (ECM) caused by infection of susceptible mice, including C57BL/6 mice, with the Plasmodium berghei ANKA parasite, have provided important clues. ECM is a severe neurovascular disease characterized by disruption of the blood-brain barrier followed by seizures, coma and death. Vascular breakdown is mediated by antigen-specific cytotoxic CD8+ T lymphocytes activated in the spleen and recruited to the brain in the presence of parasitized red blood cells. While malarial infection can clearly be affected by nutritional status of the host, whether the extremes of obesity and starvation are protective or detrimental to disease outcome remains poorly understood.
We study the effects of brief periods of dietary restriction, or reduced food intake, on neuropathology in experimental cerebral malaria. We are interested in the ability of diet to rapidly modify both innate and adaptive immune responses through modulation of host fat-derived hormones including leptin, and the requirement of conserved host nutrient sensors such as mTORC1 in this process.
Mejia P, Treviño-Villarreal JH, Hine C, Lang S, Calay E, Rogers R, Wirth D, Duraisingh M, Mitchell JR. Modulation of host adipokine leptin by short-term dietary restriction protects from experimental cerebral malaria via suppression of mTORC1. Nat Comm 2014. PMID:25636003