Review

. 2022 Nov 2;110(21):3458-3483.

doi: 10.1016/j.neuron.2022.10.020.

Microglia states and nomenclature: A field at its crossroads

Rosa C Paolicelli¹, Amanda Sierra², Beth Stevens³, Marie-Eve Tremblay⁴, Adriano Aguzzi⁵, Bahareh Ajami⁶, Ido Amit⁷, Etienne Audinat⁸, Ingo Bechmann⁹, Mariko Bennett¹⁰, Frederick Bennett¹¹, Alain Bessis¹², Knut Biber¹³, Staci Bilbo¹⁴, Mathew Blurton-Jones¹⁵, Erik Boddeke¹⁶, Dora Brites¹⁷, Bert Brône¹⁸, Guy C Brown¹⁹, Oleg Butovsky²⁰, Monica J Carson²¹, Bernardo Castellano²², Marco Colonna²³, Sally A Cowley²⁴, Colm Cunningham²⁵, Dimitrios Davalos²⁶, Philip L De Jager²⁷, Bart de Strooper²⁸, Adam Denes²⁹, Bart J L Eggen³⁰, Ukpong Eyo³¹, Elena Galea³², Sonia Garel³³, Florent Ginhoux³⁴, Christopher K Glass³⁵, Ozgun Gokce³⁶, Diego Gomez-Nicola³⁷, Berta González³⁸, Siamon Gordon³⁹, Manuel B Graeber⁴⁰, Andrew D Greenhalgh⁴¹, Pierre Gressens⁴², Melanie Greter⁴³, David H Gutmann⁴⁴, Christian Haass⁴⁵, Michael T Heneka⁴⁶, Frank L Heppner⁴⁷, Soyon Hong⁴⁸, David A Hume⁴⁹, Steffen Jung⁵⁰, Helmut Kettenmann⁵¹, Jonathan Kipnis⁵², Ryuta Koyama⁵³, Greg Lemke⁵⁴, Marina Lynch⁵⁵, Ania Majewska⁵⁶, Marzia Malcangio⁵⁷, Tarja Malm⁵⁸, Renzo Mancuso⁵⁹, Takahiro Masuda⁶⁰, Michela Matteoli⁶¹, Barry W McColl⁶², Veronique E Miron⁶³, Anna Victoria Molofsky⁶⁴, Michelle Monje⁶⁵, Eva Mracsko⁶⁶, Agnes Nadjar⁶⁷, Jonas J Neher⁶⁸, Urte Neniskyte⁶⁹, Harald Neumann⁷⁰, Mami Noda⁷¹, Bo Peng⁷², Francesca Peri⁷³, V Hugh Perry⁷⁴, Phillip G Popovich⁷⁵, Clare Pridans⁷⁶, Josef Priller⁷⁷, Marco Prinz⁷⁸, Davide Ragozzino⁷⁹, Richard M Ransohoff⁸⁰, Michael W Salter⁸¹, Anne Schaefer⁸², Dorothy P Schafer⁸³, Michal Schwartz⁸⁴, Mikael Simons⁸⁵, Cody J Smith⁸⁶, Wolfgang J Streit⁸⁷, Tuan Leng Tay⁸⁸, Li-Huei Tsai⁸⁹, Alexei Verkhratsky⁹⁰, Rommy von Bernhardi⁹¹, Hiroaki Wake⁹², Valérie Wittamer⁹³, Susanne A Wolf⁹⁴, Long-Jun Wu⁹⁵, Tony Wyss-Coray⁹⁶

Affiliations

¹ Department of Biomedical Sciences, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland. Electronic address: rosachiara.paolicelli@unil.ch.
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: amanda.sierra@ehu.eus.
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: beth.stevens@childrens.harvard.edu.
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: evetremblay@uvic.ca.
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.

PMID: 36327895
PMCID: PMC9999291
DOI: 10.1016/j.neuron.2022.10.020

Review

Microglia states and nomenclature: A field at its crossroads

Rosa C Paolicelli et al. Neuron. 2022.

. 2022 Nov 2;110(21):3458-3483.

doi: 10.1016/j.neuron.2022.10.020.

Authors

Affiliations

¹ Department of Biomedical Sciences, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland. Electronic address: rosachiara.paolicelli@unil.ch.
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: amanda.sierra@ehu.eus.
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: beth.stevens@childrens.harvard.edu.
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: evetremblay@uvic.ca.
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.

PMID: 36327895
PMCID: PMC9999291
DOI: 10.1016/j.neuron.2022.10.020

Abstract

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.

PubMed Disclaimer

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.

Figures

**Figure 1.. Microglial nomenclatures: Past and future**
Microglia have been traditionally framed into dichotomic categories, but our current integration of epigenetic, transcriptomic, metabolomic, and proteomic data favors a multidimensional integration of coexisting states.

**Figure 2.. Microglial core properties and functions**
Phagocytosis, surveillance, and capacity for releasing soluble factors (inner circle) are core properties through which microglia contribute to key biological functions (outer circle). Created with BioRender.com.

**Figure 3.. Microglial identity and states**
The identity of microglia, compared to other CNS-associated macrophages in the perivascular space, choroid plexus, and leptomeninges, is established early on from yolk-sac-derived progenitors. Once they colonize the brain parenchyma and differentiate, they can adopt multiple states depending on the particular spatiotemporal context, as shown in more detail in Figure 5. Created with BioRender.com.

**Figure 4.. Microglial transcriptomic signatures**
Recent scRNA-seq studies have identified many microglial transcriptional signatures including, but not limited to, PAM and ATM in development; DAM, MgnD, ARM, and MIMS in disease models of AD, MS, ALS, and PD; and WAM, LDAM, and HAM in aging, in both mice and human. The key upregulated (red) and downregulated (blue) genes in each signature are indicated. Created with BioRender.com.

**Figure 5.. Microglial states defined by their intrinsic and extrinsic determinants, spatiotemporal context, and layers of complexity**
Microglial states depend on intrinsic determinants (such as species, ontogeny, sex, or genetic background) as well as the specific context they inhabit, including age, spatial location, and environmental factors (such as nutrition, microbiota, pathogens, drugs, etc.). All together, these factors impinge on microglia at multiple levels (i.e., epigenomic, transcriptomic, proteomic, metabolomics, ultrastructural, and phenomic), which ultimately determine microglial functions. Created with https://BioRender.com

See this image and copyright information in PMC

References

1. Stafleu FA (1971). Linnaeus and the Linnaeans: The Spreading of their Ideas in Systematic Botany, 1735–1789 (A. Oosthoek’s Uitgeversmaat-schappij; ).
1. Charmaz K (2006). The power of names. J. Contemp. Ethnogr 35, 396–399. 10.1177/0891241606286983. - DOI
1. Guilliams M, Ginhoux F, Jakubzick C, Naik SH, Onai N, Schraml BU, Segura E, Tussiwand R, and Yona S (2014). Dendritic cells, monocytes and macrophages: a unified nomenclature based on ontogeny. Nat. Rev. Immunol 14, 571–578. 10.1038/nri3712. - DOI - PMC - PubMed
1. Murray PJ, Allen J, Biswas S, Fisher E, Gilroy D, Goerdt S, Gordon S, Hamilton J, Ivashkiv L, Lawrence T, et al. (2014). Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity 41, 14–20. 10.1016/j.immuni.2014.06.008. - DOI - PMC - PubMed
1. Yuste R, Hawrylycz M, Aalling N, Aguilar-Valles A, Arendt D, Armananzas R, Ascoli GA, Bielza C, Bokharaie V, Bergmann TB, et al. (2020). A community-based transcriptomics classification and nomenclature of neocortical cell types. Nat. Neurosci 23, 1456–1468. 10.1038/s41593-020-0685-8. - DOI - PMC - PubMed

Publication types

Actions
Actions

MeSH terms

Actions

Grants and funding

LinkOut - more resources

Full Text Sources
Research Materials
- NCI CPTC Antibody Characterization Program

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Microglia states and nomenclature: A field at its crossroads

Affiliations

Microglia states and nomenclature: A field at its crossroads

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Research Materials