title: NLRP3 Inflammasome Is Expressed and Functional in Mouse Brain Microglia but Not in Astrocytes.
abstract: Neuroinflammation is the local reaction of the brain to infection, trauma, toxic molecules or protein aggregates. The brain resident macrophages, microglia, are able to trigger an appropriate response involving secretion of cytokines and chemokines, resulting in the activation of astrocytes and recruitment of peripheral immune cells. IL-1β plays an important role in this response; yet its production and mode of action in the brain are not fully understood and its precise implication in neurodegenerative diseases needs further characterization. Our results indicate that the capacity to form a functional NLRP3 inflammasome and secretion of IL-1β is limited to the microglial compartment in the mouse brain. We were not able to observe IL-1β secretion from astrocytes, nor do they express all NLRP3 inflammasome components. Microglia were able to produce IL-1β in response to different classical inflammasome activators, such as ATP, Nigericin or Alum. Similarly, microglia secreted IL-18 and IL-1α, two other inflammasome-linked pro-inflammatory factors. Cell stimulation with α-synuclein, a neurodegenerative disease-related peptide, did not result in the release of active IL-1β by microglia, despite a weak pro-inflammatory effect. Amyloid-β peptides were able to activate the NLRP3 inflammasome in microglia and IL-1β secretion occurred in a P2X7 receptor-independent manner. Thus microglia-dependent inflammasome activation can play an important role in the brain and especially in neuroinflammatory conditions.
authors.affiliation: Life Sciences Research Unit, Faculty of Science, Technology and Communication, University of Luxembourg, Luxembourg, Luxembourg.
authors.forename: Audrey
authors.initials: A
authors.lastname: Gustin
authors.affiliation: Life Sciences Research Unit, Faculty of Science, Technology and Communication, University of Luxembourg, Luxembourg, Luxembourg.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Kirchmeyer
authors.affiliation: Life Sciences Research Unit, Faculty of Science, Technology and Communication, University of Luxembourg, Luxembourg, Luxembourg.
authors.forename: Eric
authors.initials: E
authors.lastname: Koncina
authors.affiliation: Life Sciences Research Unit, Faculty of Science, Technology and Communication, University of Luxembourg, Luxembourg, Luxembourg.
authors.forename: Paul
authors.initials: P
authors.lastname: Felten
authors.affiliation: Life Sciences Research Unit, Faculty of Science, Technology and Communication, University of Luxembourg, Luxembourg, Luxembourg.
authors.forename: Sophie
authors.initials: S
authors.lastname: Losciuto
authors.affiliation: Life Sciences Research Unit, Faculty of Science, Technology and Communication, University of Luxembourg, Luxembourg, Luxembourg.
authors.forename: Tony
authors.initials: T
authors.lastname: Heurtaux
authors.affiliation: Biochemistry Institute, University of Lausanne, Epalinges, Switzerland.
authors.forename: Aubry
authors.initials: A
authors.lastname: Tardivel
authors.affiliation: Life Sciences Research Unit, Faculty of Science, Technology and Communication, University of Luxembourg, Luxembourg, Luxembourg.
authors.forename: Paul
authors.initials: P
authors.lastname: Heuschling
authors.affiliation: Life Sciences Research Unit, Faculty of Science, Technology and Communication, University of Luxembourg, Luxembourg, Luxembourg.
authors.forename: Catherine
authors.initials: C
authors.lastname: Dostert
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000166:cytology*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D020170:Caspase 1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D058847:Inflammasomes / Q000378:metabolism*; D020382:Interleukin-18 / Q000378:metabolism; D053582:Interleukin-1alpha / Q000378:metabolism; D053583:Interleukin-1beta / Q000032:analysis / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D010446:Peptide Fragments / Q000633:toxicity; D058486:Receptors, Purinergic P2X7 / Q000378:metabolism; D051844:alpha-Synuclein / Q000494:pharmacology
chemical_list: D016229:Amyloid beta-Peptides; D002352:Carrier Proteins; D058847:Inflammasomes; D020382:Interleukin-18; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D010446:Peptide Fragments; D058486:Receptors, Purinergic P2X7; D051844:alpha-Synuclein; C074636:amyloid beta-protein (25-35); D020170:Caspase 1