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Energetic Trade-Offs and Hypometabolic States Promote Disease Tolerance.

Cell | 2019

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.

Pubmed ID: 30853215 RIS Download

Associated grants

  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK101064
  • Agency: NIH HHS, United States
    Id: S10 OD018210
  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM007618
  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK105175
  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK094641
  • Agency: NIH HHS, United States
    Id: S10 OD021505
  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK117034
  • Agency: NHLBI NIH HHS, United States
    Id: T32 HL007731

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