Host Energy Source Is Important for Disease Tolerance to Malaria

Area of Science:

• Immunology
• Metabolic research
• Infectious disease

Background:

• Pathologic infections trigger sickness behaviors, including anorexia, which are crucial host responses.
• Previous research examined anorexia in isolation, neglecting its interplay with other behaviors and host metabolism.
• Understanding the integrated effects of sickness behaviors on host energy dynamics during infection is essential.

Purpose of the Study:

• To investigate the temporal dynamics of multiple sickness behaviors and their impact on host energy metabolism during Plasmodium chabaudi malaria.
• To determine the consequences of metabolic shifts, particularly toward fatty acid oxidation and ketosis, in the context of anemia.

Main Methods:

• Utilized the Plasmodium chabaudi AJ murine malaria model.
• Monitored behavioral changes, metabolic profiles (fatty acid oxidation, ketosis), and host energy pathways.
• Administered glycolytic inhibitor 2-deoxyglucose (2DG) or glucose to infected mice.

Main Results:

• Infected mice exhibited anorexia, shifting metabolism to fatty acid oxidation and ketosis.
• Anemia in infected mice coincided with increased reliance on glycolysis due to limited oxygen for ATP production.
• Treatment with 2DG reduced survival and parasite clearance, while glucose treatment improved survival.
• Parasite loads remained unchanged, indicating effects on disease tolerance rather than resistance.

Conclusions:

• Sickness behaviors, particularly anorexia and anemia, profoundly alter host metabolism during malaria.
• Targeting glycolysis with 2DG impairs host defense, whereas glucose supplementation enhances survival.
• These findings highlight the complex relationship between host metabolism, sickness behaviors, and disease outcomes, suggesting therapeutic potential in modulating energy pathways.