Energetic Trade-Offs and Hypometabolic States Promote Disease Tolerance
| Autor: | D. Nyasha Chagwedera, Yoshitaka Sogawa, James E. Cox, Kevin Man, Tyler Van Ry, Kirthana Ganeshan, J. Alan Maschek, Yew Ann Leong, Joni Nikkanen, Ajay Chawla |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Hibernation Biology Core temperature General Biochemistry Genetics and Molecular Biology Mice 03 medical and health sciences 0302 clinical medicine Immunity Immune Tolerance Animals Homeothermy 030304 developmental biology 0303 health sciences Innate immune system Mechanism (biology) Trade offs Immunity Innate Mice Inbred C57BL Metabolism TLR4 Female Energy Metabolism Neuroscience 030217 neurology & neurosurgery Body Temperature Regulation |
| Zdroj: | Cell. 177:399-413.e12 |
| ISSN: | 0092-8674 |
| DOI: | 10.1016/j.cell.2019.01.050 |
| Popis: | Host defenses against pathogens are energetically expensive, leading ecological immunologists to postulate that they might participate in energetic trade-offs with other maintenance programs. However, the metabolic costs of immunity and the nature of physiologic trade-offs it engages are largely unknown. We report here that activation of immunity causes an energetic trade-off with the homeothermy (the stable maintenance of core temperature), resulting in hypometabolism and hypothermia. This immunity-induced physiologic trade-off was independent of sickness behaviors but required hematopoietic sensing of lipopolysaccharide (LPS) via the toll-like receptor 4 (TLR4). Metabolomics and genome-wide expression profiling revealed that distinct metabolic programs supported entry and recovery from the energy-conserving hypometabolic state. During bacterial infections, hypometabolic states, which could be elicited by competition for energy between maintenance programs or energy restriction, promoted disease tolerance. Together, our findings suggest that energy-conserving hypometabolic states, such as dormancy, might have evolved as a mechanism of tissue tolerance. |
| Databáze: | OpenAIRE |
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