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RESEARCH PRODUCT
Host-based lipid inflammation drives pathogenesis in Francisella infection
Joshua A. LiebermanKari Ann ShireyLaura BindilaRobert K. ErnstAlison J. ScottShane R. EllisRon M. A. HeerenRaissa LernerJulia Maria Postsubject
0301 basic medicineLipopolysaccharideDIVERSITYGene ExpressionLIPOPOLYSACCHARIDEhost-pathogen interactionmedicine.disease_cause01 natural sciencesMass SpectrometryVirulence factorMicechemistry.chemical_compoundlipid inflammationcyclooxygenase pathwayHETEROGENEITYFrancisellaPhospholipidsMice KnockoutMultidisciplinarybiologyTULAREMIABiological SciencesMolecular ImagingHost-Pathogen InteractionsFrancisellalipids (amino acids peptides and proteins)FemaleSignal TransductionLPSHost–pathogen interactionmicrobial pathogenesismass spectrometry imagingDinoprostoneMicrobiologyCyclooxygenase pathwayProinflammatory cytokine03 medical and health sciencesImmune systemIMAGING MASS-SPECTROMETRYmedicineAnimalsBIOSYNTHESISFrancisella novicidaInflammationMacrophages010401 analytical chemistrybacterial infections and mycosesbiology.organism_classificationSurvival AnalysisImmunity Innate0104 chemical sciencesEndotoxinsMice Inbred C57BL030104 developmental biologychemistryCyclooxygenase 2EicosanoidsGram-Negative Bacterial InfectionsSpleendescription
Mass spectrometry imaging (MSI) was used to elucidate host lipids involved in the inflammatory signaling pathway generated at the host-pathogen interface during a septic bacterial infection. Using Francisella novicida as a model organism, a bacterial lipid virulence factor (endotoxin) was imaged and identified along with host phospholipids involved in the splenic response in murine tissues. Here, we demonstrate detection and distribution of endotoxin in a lethal murine F. novicida infection model, in addition to determining the temporally and spatially resolved innate lipid inflammatory response in both 2D and 3D renderings using MSI. Further, we show that the cyclooxygenase-2-dependent lipid inflammatory pathway is responsible for lethality in F. novicida infection due to overproduction of proinflammatory effectors including prostaglandin E2. The results of this study emphasize that spatial determination of the host lipid components of the immune response is crucial to identifying novel strategies to effectively address highly pathogenic and lethal infections stemming from bacterial, fungal, and viral origins.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2017-11-21 | Proceedings of the National Academy of Sciences |