PLX5622 Reduces Disease Severity in Lethal CNS Infection by Off-Target Inhibition of Peripheral Inflammatory Monocyte Production.

Animals Mice Microglia Monocytes Organic Chemicals Receptors, Colony-Stimulating Factor / metabolism Severity of Illness Index West Nile Fever
CNS infection CSF-1R antagonism West Nile virus-induced encephalitis microglia microglia depletion monocyte-derived cells monocyte-mediated inflammation neuroinflammation

Journal

Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960

Informations de publication

Date de publication:
2022
Historique:
received: 10 01 2022
accepted: 03 03 2022
entrez: 11 4 2022
pubmed: 12 4 2022
medline: 13 4 2022
Statut: epublish

Résumé

PLX5622 is a CSF-1R inhibitor and microglia-depleting reagent, widely used to investigate the biology of this central nervous system (CNS)-resident myeloid population, but the indirect or off-target effects of this agent remain largely unexplored. In a murine model of severe neuroinflammation induced by West Nile virus encephalitis (WNE), we showed PLX5622 efficiently depleted both microglia and a sub-population of border-associated macrophages in the CNS. However, PLX5622 also significantly depleted mature Ly6C

Identifiants

DOI: 10.3389/fimmu.2022.851556 PMID: 35401512 PMC: PMC8990748
pubmed: 35401512
doi: 10.3389/fimmu.2022.851556
pmc: PMC8990748
doi:

Substances chimiques

Organic Chemicals 0
PLX5622 0
Receptors, Colony-Stimulating Factor 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

851556

Informations de copyright

Copyright © 2022 Spiteri, Ni, Ling, Macia, Campbell, Hofer and King.

Déclaration de conflit d'intérêts

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Auteurs

Alanna G Spiteri (AG)

Viral Immunopathology Laboratory, Infection, Immunity and Inflammation Research Theme, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.
Sydney Cytometry, The University of Sydney and Centenary Institute, Sydney, NSW, Australia.
Ramaciotti Facility for Human Systems Biology, The University of Sydney and Centenary Institute, Sydney, NSW, Australia.
Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.

Duan Ni (D)

Sydney Cytometry, The University of Sydney and Centenary Institute, Sydney, NSW, Australia.
Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.
Chronic Diseases Research Theme, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.

Zheng Lung Ling (ZL)

Viral Immunopathology Laboratory, Infection, Immunity and Inflammation Research Theme, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.
Sydney Cytometry, The University of Sydney and Centenary Institute, Sydney, NSW, Australia.
Ramaciotti Facility for Human Systems Biology, The University of Sydney and Centenary Institute, Sydney, NSW, Australia.
Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.

Laurence Macia (L)

Sydney Cytometry, The University of Sydney and Centenary Institute, Sydney, NSW, Australia.
Ramaciotti Facility for Human Systems Biology, The University of Sydney and Centenary Institute, Sydney, NSW, Australia.
Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.
Chronic Diseases Research Theme, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.

Iain L Campbell (IL)

School of Life and Environmental Sciences, The University of Sydney, Sydney, NSW, Australia.

Markus J Hofer (MJ)

Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.
School of Life and Environmental Sciences, The University of Sydney, Sydney, NSW, Australia.
The University of Sydney Institute for Infectious Diseases, The University of Sydney, Sydney, NSW, Australia.

Nicholas J C King (NJC)

Viral Immunopathology Laboratory, Infection, Immunity and Inflammation Research Theme, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.
Sydney Cytometry, The University of Sydney and Centenary Institute, Sydney, NSW, Australia.
Ramaciotti Facility for Human Systems Biology, The University of Sydney and Centenary Institute, Sydney, NSW, Australia.
Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.
The University of Sydney Institute for Infectious Diseases, The University of Sydney, Sydney, NSW, Australia.
The University of Sydney Nano Institute, The University of Sydney, Sydney, NSW, Australia.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › PLX5622 Reduces Disease Severity in Lethal CNS...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › PLX5622 Reduces Disease Severity in Lethal CNS...
questionsmedicales.fr › Cellules › Névroglie › Microglie › PLX5622 Reduces Disease Severity in Lethal CNS...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Phagocytes › Monocytes › PLX5622 Reduces Disease Severity in Lethal CNS...
questionsmedicales.fr › Composés chimiques organiques › PLX5622 Reduces Disease Severity in Lethal CNS...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs peptidiques › Récepteur facteur croissance › Récepteurs aux facteurs de croissance hématopoïétique › PLX5622 Reduces Disease Severity in Lethal CNS...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Collecte de données › Enquêtes et questionnaires › Enquêtes de santé › Indicateurs d'état de santé › Acuité des besoins du patient › Indice de gravité de la maladie › PLX5622 Reduces Disease Severity in Lethal CNS...
questionsmedicales.fr › Maladies du système nerveux › Encéphalite › Encéphalite infectieuse › Encéphalite virale › Encéphalite à arbovirus › Fièvre à virus West Nile › PLX5622 Reduces Disease Severity in Lethal CNS...