2019
GDF15 Is an Inflammation-Induced Central Mediator of Tissue Tolerance
Luan HH, Wang A, Hilliard B, Carvalho F, Rosen CE, Ahasic A, Herzog E, Kang I, Pisani MA, Yu S, Zhang C, Ring A, Young L, Medzhitov R. GDF15 Is an Inflammation-Induced Central Mediator of Tissue Tolerance. Cell 2019, 178: 1231-1244.e11. PMID: 31402172, PMCID: PMC6863354, DOI: 10.1016/j.cell.2019.07.033.Peer-Reviewed Original ResearchConceptsViral infectionTriglyceride metabolismImpaired cardiac functionRole of GDF15Differentiation factor 15Plasma triglyceride levelsSympathetic outflowInflammatory damageTriglyceride levelsCardiac functionInflammatory responseExogenous administrationProtective effectFactor 15GDF15Central mediatorTissue toleranceBody temperatureInfectionMetabolismSepsisInflammationAdministrationHormoneSpecific sequences of infectious challenge lead to secondary hemophagocytic lymphohistiocytosis-like disease in mice
Wang A, Pope SD, Weinstein JS, Yu S, Zhang C, Booth CJ, Medzhitov R. Specific sequences of infectious challenge lead to secondary hemophagocytic lymphohistiocytosis-like disease in mice. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 2200-2209. PMID: 30674681, PMCID: PMC6369774, DOI: 10.1073/pnas.1820704116.Peer-Reviewed Original ResearchConceptsSecondary hemophagocytic lymphohistiocytosisAssociated transcriptional programRNA sequencing analysisBone marrow-derived macrophagesTranscriptional programsTranscriptional profilingMarrow-derived macrophagesBone marrow macrophagesTranscriptional profilesNonlethal doseMitochondrial functionToll-like receptor agonistsSequencing analysisSpecific sequencesSetting of infectionGlycolytic metabolismMarrow macrophagesUseful therapeutic strategyGlycolysis inhibitorLethal stateHyperinflammatory stateHyperinflammatory responseOxidative metabolismHemophagocytic lymphohistiocytosisMortal complications
2016
Opposing Effects of Fasting Metabolism on Tissue Tolerance in Bacterial and Viral Inflammation
Wang A, Huen SC, Luan HH, Yu S, Zhang C, Gallezot JD, Booth CJ, Medzhitov R. Opposing Effects of Fasting Metabolism on Tissue Tolerance in Bacterial and Viral Inflammation. Cell 2016, 166: 1512-1525.e12. PMID: 27610573, PMCID: PMC5555589, DOI: 10.1016/j.cell.2016.07.026.Peer-Reviewed Original ResearchConceptsNutritional supplementationMagnitude of inflammationRole of anorexiaViral inflammationViral sepsisStereotypic behavioral responsesAcute infectionBacterial sepsisInfluenza infectionInflammatory stateSickness behaviorViral infectionFamiliar symptomsGlucose utilizationHost defenseAnorexiaInfectionViral modelSepsisTissue toleranceInflammationSocial withdrawalSupplementationMetabolic requirementsPathogen load