Impact of inflammatory preconditioning on murine microglial proteome response induced by focal ischemic brain injury

Preconditioning with lipopolysaccharide (LPS) induces neuroprotection against subsequent cerebral ischemic injury, mainly involving innate immune pathways. Microglia are resident immune cells of the central nervous system (CNS) that respond early to danger signals through memory-like differential re...

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Main Authors: Dario Lucas Helbing, Fabienne Haas, Emilio Cirri, Norman Rahnis, Therese Thuy Dung Dau, Erika Kelmer Sacramento, Nova Oraha, Leopold Böhm, Trim Lajqi, Pascal Fehringer, Helen Morrison, Reinhard Bauer
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-04-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2024.1227355/full
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author Dario Lucas Helbing
Dario Lucas Helbing
Dario Lucas Helbing
Dario Lucas Helbing
Dario Lucas Helbing
Fabienne Haas
Emilio Cirri
Norman Rahnis
Therese Thuy Dung Dau
Erika Kelmer Sacramento
Nova Oraha
Nova Oraha
Leopold Böhm
Leopold Böhm
Leopold Böhm
Trim Lajqi
Pascal Fehringer
Helen Morrison
Helen Morrison
Reinhard Bauer
author_facet Dario Lucas Helbing
Dario Lucas Helbing
Dario Lucas Helbing
Dario Lucas Helbing
Dario Lucas Helbing
Fabienne Haas
Emilio Cirri
Norman Rahnis
Therese Thuy Dung Dau
Erika Kelmer Sacramento
Nova Oraha
Nova Oraha
Leopold Böhm
Leopold Böhm
Leopold Böhm
Trim Lajqi
Pascal Fehringer
Helen Morrison
Helen Morrison
Reinhard Bauer
author_sort Dario Lucas Helbing
collection DOAJ
description Preconditioning with lipopolysaccharide (LPS) induces neuroprotection against subsequent cerebral ischemic injury, mainly involving innate immune pathways. Microglia are resident immune cells of the central nervous system (CNS) that respond early to danger signals through memory-like differential reprogramming. However, the cell-specific molecular mechanisms underlying preconditioning are not fully understood. To elucidate the distinct molecular mechanisms of preconditioning on microglia, we compared these cell-specific proteomic profiles in response to LPS preconditioning and without preconditioning and subsequent transient focal brain ischemia and reperfusion, – using an established mouse model of transient focal brain ischemia and reperfusion. A proteomic workflow, based on isolated microglia obtained from mouse brains by cell sorting and coupled to mass spectrometry for identification and quantification, was applied. Our data confirm that LPS preconditioning induces marked neuroprotection, as indicated by a significant reduction in brain infarct volume. The established brain cell separation method was suitable for obtaining an enriched microglial cell fraction for valid proteomic analysis. The results show a significant impact of LPS preconditioning on microglial proteome patterns by type I interferons, presumably driven by the interferon cluster regulator proteins signal transducer and activator of transcription1/2 (STAT1/2).
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spelling doaj.art-af9983664f5e42a9b7a04451c7f455602024-04-09T13:01:47ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-04-011510.3389/fimmu.2024.12273551227355Impact of inflammatory preconditioning on murine microglial proteome response induced by focal ischemic brain injuryDario Lucas Helbing0Dario Lucas Helbing1Dario Lucas Helbing2Dario Lucas Helbing3Dario Lucas Helbing4Fabienne Haas5Emilio Cirri6Norman Rahnis7Therese Thuy Dung Dau8Erika Kelmer Sacramento9Nova Oraha10Nova Oraha11Leopold Böhm12Leopold Böhm13Leopold Böhm14Trim Lajqi15Pascal Fehringer16Helen Morrison17Helen Morrison18Reinhard Bauer19Institute of Molecular Cell Biology, Jena University Hospital, Friedrich Schiller University, Jena, GermanyLeibniz Institute on Aging, Fritz Lipmann Institute, Jena, GermanyDepartment of Psychiatry and Psychotherapy, Jena University Hospital, Friedrich Schiller University Jena, Jena, GermanyCenter for Intervention and Research on Adaptive and Maladaptive Brain Circuits Underlying Mental Health (C-I-R-C), Jena-Magdeburg-Halle, Jena, GermanyGerman Center for Mental Health (DZPG), Site Halle-Jena-Magdeburg, Jena, GermanyInstitute of Molecular Cell Biology, Jena University Hospital, Friedrich Schiller University, Jena, GermanyLeibniz Institute on Aging, Fritz Lipmann Institute, Jena, GermanyLeibniz Institute on Aging, Fritz Lipmann Institute, Jena, GermanyLeibniz Institute on Aging, Fritz Lipmann Institute, Jena, GermanyLeibniz Institute on Aging, Fritz Lipmann Institute, Jena, GermanyInstitute of Molecular Cell Biology, Jena University Hospital, Friedrich Schiller University, Jena, GermanyLeibniz Institute on Aging, Fritz Lipmann Institute, Jena, GermanyInstitute of Molecular Cell Biology, Jena University Hospital, Friedrich Schiller University, Jena, GermanyLeibniz Institute on Aging, Fritz Lipmann Institute, Jena, GermanyDepartment of Microbiology and Hospital Hygiene, Bundeswehr Central Hospital Koblenz, Koblenz, GermanyDepartment of Neonatology, Heidelberg University Children’s Hospital, Heidelberg, GermanyInstitute of Molecular Cell Biology, Jena University Hospital, Friedrich Schiller University, Jena, GermanyLeibniz Institute on Aging, Fritz Lipmann Institute, Jena, GermanyFaculty of Biological Sciences, Friedrich-Schiller University, Jena, GermanyInstitute of Molecular Cell Biology, Jena University Hospital, Friedrich Schiller University, Jena, GermanyPreconditioning with lipopolysaccharide (LPS) induces neuroprotection against subsequent cerebral ischemic injury, mainly involving innate immune pathways. Microglia are resident immune cells of the central nervous system (CNS) that respond early to danger signals through memory-like differential reprogramming. However, the cell-specific molecular mechanisms underlying preconditioning are not fully understood. To elucidate the distinct molecular mechanisms of preconditioning on microglia, we compared these cell-specific proteomic profiles in response to LPS preconditioning and without preconditioning and subsequent transient focal brain ischemia and reperfusion, – using an established mouse model of transient focal brain ischemia and reperfusion. A proteomic workflow, based on isolated microglia obtained from mouse brains by cell sorting and coupled to mass spectrometry for identification and quantification, was applied. Our data confirm that LPS preconditioning induces marked neuroprotection, as indicated by a significant reduction in brain infarct volume. The established brain cell separation method was suitable for obtaining an enriched microglial cell fraction for valid proteomic analysis. The results show a significant impact of LPS preconditioning on microglial proteome patterns by type I interferons, presumably driven by the interferon cluster regulator proteins signal transducer and activator of transcription1/2 (STAT1/2).https://www.frontiersin.org/articles/10.3389/fimmu.2024.1227355/fullmiceinflammatory preconditioningneuroinflammationischemic strokemicrogliatype I interferons
spellingShingle Dario Lucas Helbing
Dario Lucas Helbing
Dario Lucas Helbing
Dario Lucas Helbing
Dario Lucas Helbing
Fabienne Haas
Emilio Cirri
Norman Rahnis
Therese Thuy Dung Dau
Erika Kelmer Sacramento
Nova Oraha
Nova Oraha
Leopold Böhm
Leopold Böhm
Leopold Böhm
Trim Lajqi
Pascal Fehringer
Helen Morrison
Helen Morrison
Reinhard Bauer
Impact of inflammatory preconditioning on murine microglial proteome response induced by focal ischemic brain injury
Frontiers in Immunology
mice
inflammatory preconditioning
neuroinflammation
ischemic stroke
microglia
type I interferons
title Impact of inflammatory preconditioning on murine microglial proteome response induced by focal ischemic brain injury
title_full Impact of inflammatory preconditioning on murine microglial proteome response induced by focal ischemic brain injury
title_fullStr Impact of inflammatory preconditioning on murine microglial proteome response induced by focal ischemic brain injury
title_full_unstemmed Impact of inflammatory preconditioning on murine microglial proteome response induced by focal ischemic brain injury
title_short Impact of inflammatory preconditioning on murine microglial proteome response induced by focal ischemic brain injury
title_sort impact of inflammatory preconditioning on murine microglial proteome response induced by focal ischemic brain injury
topic mice
inflammatory preconditioning
neuroinflammation
ischemic stroke
microglia
type I interferons
url https://www.frontiersin.org/articles/10.3389/fimmu.2024.1227355/full
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