Energetic Trade-Offs and Hypometabolic States Promote Disease Tolerance.

Autor:	Ganeshan K; Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA., Nikkanen J; Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA., Man K; Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA., Leong YA; Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA; Centre for Inflammatory Diseases, Department of Medicine, School of Clinical Sciences at Monash Health, Monash University, Melbourne, VIC, Australia., Sogawa Y; Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA., Maschek JA; Department of Biochemistry, University of Utah, Salt Lake City, UT 84112, USA; Metabolomics Core Research Facility, University of Utah, Salt Lake City, UT 84112, USA., Van Ry T; Department of Biochemistry, University of Utah, Salt Lake City, UT 84112, USA; Metabolomics Core Research Facility, University of Utah, Salt Lake City, UT 84112, USA., Chagwedera DN; Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA., Cox JE; Department of Biochemistry, University of Utah, Salt Lake City, UT 84112, USA; Metabolomics Core Research Facility, University of Utah, Salt Lake City, UT 84112, USA., Chawla A; Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA; Departments of Physiology and Medicine, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: ajay.chawla@ucsf.edu.
Jazyk:	angličtina
Zdroj:	Cell [Cell] 2019 Apr 04; Vol. 177 (2), pp. 399-413.e12. Date of Electronic Publication: 2019 Mar 07.
DOI:	10.1016/j.cell.2019.01.050
Abstrakt:	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. (Copyright © 2019 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu