Dietary restriction protects against experimental cerebral malaria via leptin modulation and T-cell mTORC1 suppression
| Autor: | Manoj T. Duraisingh, Christopher Hine, James R. Mitchell, Samantha Lang, Eylul Harputlugil, Dyann F. Wirth, Rick A. Rogers, Pedro Mejia, J. Humberto Treviño-Villarreal, Ediz S. Calay |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
CD4-Positive T-Lymphocytes
Leptin medicine.medical_specialty media_common.quotation_subject T cell Malaria Cerebral General Physics and Astronomy Adipokine Spleen mTORC1 CD8-Positive T-Lymphocytes Mechanistic Target of Rapamycin Complex 1 Biology Real-Time Polymerase Chain Reaction Article General Biochemistry Genetics and Molecular Biology Mice Immune system Internal medicine medicine Animals Caloric Restriction media_common Sirolimus Multidisciplinary TOR Serine-Threonine Kinases Appetite General Chemistry Mice Inbred C57BL medicine.anatomical_structure Endocrinology Cerebral Malaria Multiprotein Complexes Immunology Body Composition Female |
| Zdroj: | Nature communications |
| ISSN: | 2041-1723 |
| Popis: | Host nutrition can affect the outcome of parasitic diseases through metabolic effects on host immunity and/or the parasite. Here we show that modulation of mouse immunometabolism through brief restriction of food intake (dietary restriction, DR) prevents neuropathology in experimental cerebral malaria (ECM). While no effects are detected on parasite growth, DR reduces parasite accumulation in peripheral tissues including the brain, and increases clearance in the spleen. Leptin, a host-derived adipokine linking appetite, energy balance and immune function, is required for ECM pathology and its levels are reduced upon DR. Recombinant leptin abrogates DR benefits, while pharmacological or genetic inhibition of leptin signalling protects against ECM. DR reduces mTORC1 activity in T cells, and this effect is abrogated upon leptin administration. Furthermore, mTORC1 inhibition with rapamycin prevents ECM pathology. Our results suggest that leptin and mTORC1 provide a novel mechanistic link between nutrition, immunometabolism and ECM pathology, with potential therapeutic implications for cerebral malaria. |
| Databáze: | OpenAIRE |
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