Microglia states and nomenclature: A field at its crossroads
Neuron. 2022-11-01; 110(21): 3458-3483
DOI: 10.1016/j.neuron.2022.10.020
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Paolicelli RC(1), Sierra A(2), Stevens B(3), Tremblay ME(4), Aguzzi A(5), Ajami
B(6), Amit I(7), Audinat E(8), Bechmann I(9), Bennett M(10), Bennett F(11),
Bessis A(12), Biber K(13), Bilbo S(14), Blurton-Jones M(15), Boddeke E(16),
Brites D(17), Brône B(18), Brown GC(19), Butovsky O(20), Carson MJ(21),
Castellano B(22), Colonna M(23), Cowley SA(24), Cunningham C(25), Davalos D(26),
De Jager PL(27), de Strooper B(28), Denes A(29), Eggen BJL(30), Eyo U(31), Galea
E(32), Garel S(33), Ginhoux F(34), Glass CK(35), Gokce O(36), Gomez-Nicola D(37),
González B(38), Gordon S(39), Graeber MB(40), Greenhalgh AD(41), Gressens P(42),
Greter M(43), Gutmann DH(44), Haass C(45), Heneka MT(46), Heppner FL(47), Hong
S(48), Hume DA(49), Jung S(50), Kettenmann H(51), Kipnis J(52), Koyama R(53),
Lemke G(54), Lynch M(55), Majewska A(56), Malcangio M(57), Malm T(58), Mancuso
R(59), Masuda T(60), Matteoli M(61), McColl BW(62), Miron VE(63), Molofsky
AV(64), Monje M(65), Mracsko E(66), Nadjar A(67), Neher JJ(68), Neniskyte U(69),
Neumann H(70), Noda M(71), Peng B(72), Peri F(73), Perry VH(74), Popovich PG(75),
Pridans C(76), Priller J(77), Prinz M(78), Ragozzino D(79), Ransohoff RM(80),
Salter MW(81), Schaefer A(82), Schafer DP(83), Schwartz M(84), Simons M(85),
Smith CJ(86), Streit WJ(87), Tay TL(88), Tsai LH(89), Verkhratsky A(90), von
Bernhardi R(91), Wake H(92), Wittamer V(93), Wolf SA(94), Wu LJ(95), Wyss-Coray
T(96).
Author information:
(1)Department of Biomedical Sciences, Faculty of Biology and Medicine, University
of Lausanne, Lausanne, Switzerland. Electronic address:
.
(2)Achucarro Basque Center for Neuroscience, Glial Cell Biology Lab, Leioa,
Spain; Department of Neuroscience, University of the Basque Country EHU/UPV,
Leioa, Spain; Ikerbasque Foundation, Bilbao, Spain. Electronic address:
.
(3)Broad Institute of MIT and Harvard, Cambridge, MA, USA; Howard Hughes Medical
Institute, (HHMI), MD, USA; Boston Children’s Hospital, Boston, MA, USA.
Electronic address: .
(4)Centre de recherche du CHU de Québec-Université Laval, Québec City, QC,
Canada; Department of Neurology and Neurosurgery, McGill University, Montréal,
QC, Canada; Division of Medical Sciences, University of Victoria, Victoria, BC,
Canada; Center for Advanced Materials and Related Technology (CAMTEC), University
of Victoria, Victoria, BC, Canada; Department of Biochemistry and Molecular
Biology, University of British Columbia, Vancouver, BC, Canada. Electronic
address: .
(5)Institute of Neuropathology, University of Zurich, Zurich, Switzerland.
(6)Department of Molecular Microbiology & Immunology, Department of Behavioral
and Systems Neuroscience, Oregon Health & Science University School of Medicine,
Portland, OR, USA.
(7)Department of Systems Immunology, Weizmann Institute of Science, Rehovot,
Israel.
(8)Institut de Génomique Fonctionnelle, Université de Montpellier, CNRS, INSERM,
Montpellier, France.
(9)Institute of Anatomy, University of Leipzig, Leipzig, Germany.
(10)Children’s Hospital of Philadelphia, Department of Psychiatry, Department of
Pediatrics, Division of Child Neurology, Philadelphia, PA, USA.
(11)Children’s Hospital of Philadelphia, University of Pennsylvania,
Philadelphia, PA, USA.
(12)École Normale Supérieure, Institut National de la Santé et de la Recherche
Médicale, Centre National de la Recherche Scientifique, Paris Sciences et Lettres
Research University, Paris, France.
(13)Neuroscience Discovery, AbbVie Deutschland GmbH, Ludwigshafen, Germany.
(14)Departments of Psychology & Neuroscience, Neurobiology, and Cell Biology,
Duke University, Durham, NC, USA.
(15)Center for the Neurobiology of Learning and Memory, UCI MIND, University of
California, Irvine, CA, USA.
(16)Department Biomedical Sciences of Cells & Systems, Section Molecular
Neurobiology, University of Groningen, University Medical Center, Groningen, the
Netherlands.
(17)Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy,
Universidade de Lisboa, Lisbon, Portugal.
(18)BIOMED Research Institute, University of Hasselt, Hasselt, Belgium.
(19)Department of Biochemistry, University of Cambridge, Cambridge, UK.
(20)Ann Romney Center for Neurologic Diseases, Department Neurology, Brigham and
Women’s Hospital, Harvard Medical School, Boston, MA, USA.
(21)Center for Glial-Neuronal Interactions, Division of Biomedical Sciences,
University of California Riverside School of Medicine, Riverside, CA, USA.
(22)Unidad de Histología Medica, Depto. Biología Celular, Fisiología e
Inmunología, Barcelona, Spain; Instituto de Neurociencias, Universidad Autónoma
de Barcelona, Barcelona, Spain.
(23)Department of Pathology and Immunology, Washington University School of
Medicine in St. Louis, St. Louis, MO, USA.
(24)James and Lillian Martin Centre for Stem Cell Research, Sir William Dunn
School of Pathology, University of Oxford, Oxford, UK.
(25)School of Biochemistry & Immunology, Trinity Biomedical Sciences Institute,
Trinity College, Dublin, Republic of Ireland; Trinity College Institute of
Neuroscience, Trinity College, Dublin, Republic of Ireland.
(26)Department of Neurosciences, Lerner Research Institute, Cleveland Clinic,
Cleveland, OH, USA; Department of Molecular Medicine, Cleveland Clinic Lerner
College of Medicine, Case Western Reserve University, Cleveland, OH, USA.
(27)Center for Translational & Computational Neuroimmunology, Department of
Neurology, Columbia University Irving Medical Center, New York, NY, USA; Taub
Institute for Research on Alzheimer’s Disease and the Aging Brain, Columbia
University Irving Medical Center, New York, NY, USA.
(28)UK Dementia Research Institute at University College London, London, UK;
Vlaams Instituut voor Biotechnologie at Katholieke Universiteit Leuven, Leuven,
Belgium.
(29)”Momentum” Laboratory of Neuroimmunology, Institute of Experimental Medicine,
Budapest, Hungary.
(30)Department of Biomedical Sciences of Cells & Systems, section Molecular
Neurobiology, University of Groningen, Groningen, the Netherlands; University
Medical Center Groningen, Groningen, the Netherlands.
(31)Department of Neuroscience, Center for Brain Immunology and Glia, University
of Virginia School of Medicine, Charlottesville, VA, USA.
(32)Institut de Neurociències and Departament de Bioquímica, Unitat de
Bioquímica, Universitat Autònoma de Barcelona, Barcelona, Spain; ICREA,
Barcelona, Spain.
(33)Institut de Biologie de l’ENS (IBENS), Département de Biologie, École Normale
Supérieure, CNRS, INSERM, Paris, France; College de France, Paris, France.
(34)Singapore Immunology Network (SIgN), Agency for Science, Technology and
Research (A(∗)STAR), Singapore, Singapore.
(35)University of California San Diego School of Medicine, La Jolla, CA, USA.
(36)Institute for Stroke and Dementia Research, Ludwig Maximillian’s University
of Munich, Munich, Germany.
(37)School of Biological Sciences, University of Southampton, Southampton General
Hospital, Southampton, UK.
(38)Unidad de Histología Medica, Depto. Biología Celular, Fisiología e
Inmunología and Instituto de Neurociencias, Universidad Autónoma de Barcelona,
Barcelona, Spain.
(39)Chang Gung University, Taoyuan City, Taiwan (ROC); Sir William Dunn School of
Pathology, Oxford, UK.
(40)Ken Parker Brain Tumour Research Laboratories, Brain and Mind Centre, Faculty
of Medicine and Health, The University of Sydney, Camperdown, NSW, Australia.
(41)Lydia Becker Institute of Immunology and Inflammation, Geoffrey Jefferson
Brain Research Centre, Division of Infection, Immunity & Respiratory Medicine,
Faculty of Biology, Medicine and Health, The University of Manchester,
Manchester, UK.
(42)Université Paris Cité, Inserm, NeuroDiderot, 75019 Paris, France.
(43)Institute of Experimental Immunology, University of Zurich, Zurich,
Switzerland.
(44)Department of Neurology, Washington University School of Medicine, St. Louis,
MO, USA.
(45)Division of Metabolic Biochemistry, Faculty of Medicine, Biomedical Center
(BMC), Ludwig-Maximilians-Universität Munchen, Munich, Germany; German Center for
Neurodegenerative Diseases (DZNE), Munich, Germany; Munich Cluster for Systems
Neurology (SyNergy); Munich, Germany.
(46)Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Belvaux,
Luxembourg.
(47)Department of Neuropathology, Charité – Universitätsmedizin Berlin, Berlin,
Germany.
(48)UK Dementia Research Institute at University College London, London, UK.
(49)Mater Research Institute-University of Queensland, Brisbane, QLD, Australia.
(50)Department of Immunology and Regenerative Biology, Weizmann Institute of
Science, Rehovot, Israel.
(51)Max-Delbrück Center for Molecular Medicine, Berlin, Germany; Shenzhen
Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
(52)Center for Brain Immunology and Glia (BIG), Department of Pathology and
Immunology, Washington University in St. Louis, St. Louis, MO, USA.
(53)Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical
Sciences, The University of Tokyo, Tokyo, Japan.
(54)MNL-L, The Salk Institute for Biological Studies, La Jolla, CA, USA.
(55)Trinity College Institute of Neuroscience, Trinity College, Dublin, Republic
of Ireland.
(56)Department of Neuroscience, University of Rochester, Rochester, NY, USA.
(57)Wolfson Centre for Age-Related Diseases, Institute of Psychiatry, Psychology
and Neuroscience, King’s College London, London, UK.
(58)University of Eastern Finland, Kuopio, Finland.
(59)Microglia and Inflammation in Neurological Disorders (MIND) Lab, VIB Center
for Molecular Neurology, VIB, Antwerp, Belgium; Department of Biomedical
Sciences, University of Antwerp, Antwerp, Belgium.
(60)Department of Molecular and System Pharmacology, Graduate School of
Pharmaceutical Sciences, Kyushu University, Japan.
(61)Humanitas University, Department of Biomedical Sciences, Milan, Italy.
(62)UK Dementia Research Institute, Centre for Discovery Brain Sciences,
University of Edinburgh, Edinburgh BioQuarter, Edinburgh, UK.
(63)MRC Centre for Reproductive Health, The Queen’s Medical Research Institute,
Edinburgh BioQuarter, Edinburgh, UK; UK Dementia Research Institute at the
University of Edinburgh, Edinburgh BioQuarter, Edinburgh, UK.
(64)University of California, San Francisco, CA, USA.
(65)Howard Hughes Medical Institute, (HHMI), MD, USA; Department of Neurology and
Neurological Sciences, Stanford University School of Medicine, Stanford
University, Stanford, CA, USA.
(66)Roche Innovation Center, Basel, Switzerland.
(67)Neurocentre Magendie, University of Bordeaux, Bordeaux, France; Institut
Universitaire de France (IUF), Paris, France.
(68)German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany;
Department of Cellular Neurology, Hertie Institute for Clinical Brain Research,
University of Tübingen, Tübingen, Germany.
(69)VU LSC-EMBL Partnership for Genome Editing Technologies, Life Sciences
Center, Vilnius University, Vilnius, Lithuania; Institute of Biosciences, Life
Sciences Center, Vilnius University, Vilnius, Lithuania.
(70)Institute of Reconstructive Neurobiology, Medical Faculty and University
Hospital of Bonn, University of Bonn, Bonn, Germany.
(71)Laboratory of Pathophysiology, Graduate School of Pharmaceutical Sciences,
Kyushu University, Fukuoka, Japan; Institute of Mitochondrial Biology and
Medicine of Xi’an Jiaotong University School of Life Science and Technology,
Xi’an, China.
(72)Department of Neurosurgery, Huashan Hospital, Institute for Translational
Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers
Center for Brain Science, Fudan University, Shanghai, China.
(73)Department of Molecular Life Sciences, University of Zurich, Zurich,
Switzerland.
(74)UK Dementia Research Institute, University College London, London, UK; School
of Biological Sciences, University of Southampton, Southampton, UK.
(75)Department of Neuroscience, College of Medicine, The Ohio State University,
Columbus, OH, USA.
(76)University of Edinburgh, Centre for Inflammation Research, Edinburgh, UK.
(77)Department of Psychiatry & Psychotherapy, School of Medicine, Technical
University of Munich, Munich, Germany; Charité – Universitätsmedizin Berlin and
DZNE, Berlin, Germany; University of Edinburgh and UK DRI, Edinburgh, UK.
(78)Institute of Neuropathology, Faculty of Medicine, University of Freiburg,
Freiburg, Germany; Center for Basics in NeuroModulation (NeuroModulBasics),
Faculty of Medicine, University of Freiburg, Freiburg, Germany; Signalling
Research Centres BIOSS and CIBSS, University of Freiburg, Freiburg, Germany.
(79)Department of Physiology and Pharmacology, Sapienza University of Rome, Rome,
Italy; Santa Lucia Foundation (IRCCS Fondazione Santa Lucia), Rome, Italy.
(80)Third Rock Ventures, Boston, MA, USA.
(81)Hospital for Sick Children, Toronto, ON, Canada; University of Toronto,
Toronto, ON, Canada.
(82)Nash Family Department of Neuroscience, Center for Glial Biology, Friedman
Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Max
Planck Institute for Biology of Ageing, Koeln, Germany.
(83)Department of Neurobiology, Brudnick Neuropsychiatric Research Institute,
University of Massachusetts Medical School, Worcester, MA, USA.
(84)Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
(85)Institute of Neuronal Cell Biology, Technical University Munich, German
Center for Neurodegenerative Diseases, Munich, Germany.
(86)Galvin Life Science Center, University of Notre Dame, Indianapolis, IN, USA.
(87)Department of Neuroscience, University of Florida, Gainesville, FL, USA.
(88)Faculty of Biology, University of Freiburg, Freiburg, Germany;
BrainLinks-BrainTools Centre, University of Freiburg, Freiburg, Germany; Freiburg
Institute of Advanced Studies, University of Freiburg, Freiburg, Germany;
Department of Biology, Boston University, Boston, MA, USA; Department of Anatomy
and Neurobiology, Boston University School of Medicine, Boston, MA, USA.
(89)Broad Institute of MIT and Harvard, Cambridge, MA, USA; Picower Institute for
Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, USA;
Department of Brain and Cognitive Sciences, Massachusetts Institute of
Technology, Cambridge, MA, USA.
(90)Achucarro Basque Center for Neuroscience, Glial Cell Biology Lab, Leioa,
Spain; Department of Neuroscience, University of the Basque Country EHU/UPV,
Leioa, Spain; Faculty of Biology, Medicine and Health, The University of
Manchester, Manchester, UK.
(91)Faculty of Medicine and Science, Universidad San Sebastian, Santiago, Chile.
(92)Department of Anatomy and Molecular Cell Biology, Graduate School of
Medicine, Nagoya University, Nagoya, Japan.
(93)Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire
(IRIBHM), Université Libre de Bruxelles (ULB), Brussels, Belgium; ULB
Neuroscience Institute (UNI), Université Libre de Bruxelles (ULB), Brussels,
Belgium.
(94)Charité Universitätsmedizin, Experimental Ophthalmology and Neuroimmunology,
Berlin, Germany.
(95)Department of Neurology and Department of Immunology, Mayo Clinic, Rochester,
MN, USA.
(96)Department of Neurology and Neurological Sciences, Stanford University School
of Medicine, Stanford University, Stanford, CA, USA.
Microglial research has advanced considerably in recent decades yet has been
constrained by a rolling series of dichotomies such as “resting versus activated”
and “M1 versus M2.” This dualistic classification of good or bad microglia is
inconsistent with the wide repertoire of microglial states and functions in
development, plasticity, aging, and diseases that were elucidated in recent
years. New designations continuously arising in an attempt to describe the
different microglial states, notably defined using transcriptomics and
proteomics, may easily lead to a misleading, although unintentional, coupling of
categories and functions. To address these issues, we assembled a group of
multidisciplinary experts to discuss our current understanding of microglial
states as a dynamic concept and the importance of addressing microglial function.
Here, we provide a conceptual framework and recommendations on the use of
microglial nomenclature for researchers, reviewers, and editors, which will serve
as the foundations for a future white paper.
Copyright © 2022 Elsevier Inc. All rights reserved.
DOI: 10.1016/j.neuron.2022.10.020
PMID: 36327895 [Indexed for MEDLINE]
Conflict of interest statement: Declaration of interests B.A. is the shareholder
and member of scientific advisory board of Tranquis Therapeutics. K.B. is an
employee and shareholder of AbbVie. M.C. receives research support from Vigil, is
a member of the scientific advisory board of Vigil, and has a patent on TREM2.
S.C. is a recipient of research funding from Eli Lilly and Company. C.C. is a
member of the advisory board of Exalys Therapeutics and is the recipient of a
research grant from IONIS therapeutics. B.D.S. is occasionally consulting for
different companies. He is founding scientist of Augustin TX and of Muna TX. He
is also shareholder of Muna TX. C.H. collaborates with Denali Therapeutics. C.H.
is chief advisor of ISAR Bioscience and a member of the advisory board of
AviadoBio. J.K. is a scientific advisor and collaborator with PureTech. T.M. is a
cofounder of REGAIN Therapeutics, owner of a provisional patent on compositions
and methods for treatment and/or prophylaxis of proteinopathies, and owner of a
provisional patent on preventing or reverting abnormal amyloid deposition. R.M.
has scientific collaborations with Alector, Nodthera, and Alchemab and is a
consultant for Sanofi. B.M. has received consultancy fees from AstraZeneca. A.
Sierra is a recipient of a research grant from Hoffmann La Roche.