Journal ArticleDOI
Ontogeny and homeostasis of CNS myeloid cells.
TLDR
Studies using cell-specific targeting, in vivo imaging, single-cell expression analysis and other sophisticated tools have increased the depth of knowledge of this immune-cell compartment and call for reevaluation of the traditional views on the origin, fate and function of distinct CNS myeloid subsets.Abstract:
Myeloid cells in the central nervous system (CNS) represent a heterogeneous class of innate immune cells that contribute to the maintenance of tissue homeostasis differentially during development and adulthood. The subsets of CNS myeloid cells identified so far, including parenchymal microglia and non-parenchymal meningeal, perivascular and choroid-plexus macrophages, as well as disease-associated monocytes, have classically been distinguished on the basis of their surface epitope expression, localization and morphology. However, studies using cell-specific targeting, in vivo imaging, single-cell expression analysis and other sophisticated tools have now increased the depth of knowledge of this immune-cell compartment and call for reevaluation of the traditional views on the origin, fate and function of distinct CNS myeloid subsets. The concepts of CNS macrophage biology that are emerging from these new insights have broad implications for the understanding and treatment of CNS diseases.read more
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Neurons under T Cell Attack Coordinate Phagocyte-Mediated Synaptic Stripping.
Giovanni Di Liberto,Stanislav Pantelyushin,Mario Kreutzfeldt,Nicolas Page,Stefano Musardo,Roland Coras,Karin Steinbach,Ilena Vincenti,Bogna Klimek,Thomas Lingner,Gabriela Salinas,Nathalie Lin-Marq,Ori Staszewski,Marta Joana Costa Jordão,Ingrid Wagner,Kristof Egervari,Kristof Egervari,Matthias Mack,Camilla Bellone,Ingmar Blümcke,Marco Prinz,Daniel D. Pinschewer,Doron Merkler,Doron Merkler +23 more
TL;DR: An active role of neurons is uncovered in coordinating phagocyte-mediated synaptic loss in a murine model of encephalitis caused by CD8+ T cells targeting antigenic neurons and is highlighted as critical steps in this process that are amenable to pharmacological interventions.
Journal ArticleDOI
Comprehensive gene expression meta-analysis identifies signature genes that distinguish microglia from peripheral monocytes/macrophages in health and glioma
Verena Haage,Marcus Semtner,Ramon Vidal,Daniel Hernández,Winnie W. Pong,Zhihong Chen,Dolores Hambardzumyan,Vincent Magrini,Amy Ly,Jason Walker,Elaine R. Mardis,Philipp Mertins,Sascha Sauer,Helmut Kettenmann,David H. Gutmann,David H. Gutmann +15 more
TL;DR: A large meta-analytic approach facilitated the discovery of a robust set of microglia and peripheral monocyte/macrophage expression markers to discriminate these monocyte populations in both health and disease.
Journal ArticleDOI
Immune responses in stroke: how the immune system contributes to damage and healing after stroke and how this knowledge could be translated to better cures?
Aditya Rayasam,Martin Hsu,Julie A. Kijak,Lee Kissel,Gianna Hernandez,Matyas Sandor,Zsuzsanna Fabry +6 more
TL;DR: Advances in the understanding of the complex innate and adaptive immune responses in stroke; mechanisms of immune cell‐mediated and factor‐mediated vascular and tissue injury; immunity‐induced tissue repair; and the importance of modulating immunity in stroke are discussed.
Journal ArticleDOI
Siglec‐H is a microglia‐specific marker that discriminates microglia from CNS‐associated macrophages and CNS‐infiltrating monocytes
Hiroyuki Konishi,Masaaki Kobayashi,Taikan Kunisawa,Kenta Imai,Akira Sayo,Bernard Malissen,Paul R. Crocker,Katsuaki Sato,Hiroshi Kiyama +8 more
TL;DR: It is demonstrated that Siglec‐H is an authentic marker for microglia in mice by immunohistochemistry using a SigleC‐H‐specific antibody and that the Siglech gene locus is a feasible site for specific targeting of microglian gene manipulation in the nervous system.
Journal ArticleDOI
An updated assessment of microglia depletion: current concepts and future directions.
TL;DR: The highly plastic and diverse phenotypes of microglia are highlighted and lessons learned from microglian depletion approaches are outlined, thus holding promise for designing strategies to resolve neuroinflammation and promote recovery.
References
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Fate Mapping Analysis Reveals That Adult Microglia Derive from Primitive Macrophages
Florent Ginhoux,Florent Ginhoux,Melanie Greter,Marylene Leboeuf,Sayan Nandi,Peter See,Solen Gokhan,Mark F. Mehler,Simon J. Conway,Lai Guan Ng,E. Richard Stanley,Igor M. Samokhvalov,Miriam Merad +12 more
TL;DR: Results identify microglia as an ontogenically distinct population in the mononuclear phagocyte system and have implications for the use of embryonically derived microglial progenitors for the treatment of various brain disorders.
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Cell types in the mouse cortex and hippocampus revealed by single-cell RNA-seq
Amit Zeisel,Ana B. Muñoz-Manchado,Simone Codeluppi,Peter Lönnerberg,Gioele La Manno,Anna Juréus,Sueli Marques,Hermany Munguba,Liqun He,Christer Betsholtz,Christer Betsholtz,Charlotte Rolny,Gonçalo Castelo-Branco,Jens Hjerling-Leffler,Sten Linnarsson +14 more
TL;DR: Large-scale single-cell RNA sequencing is used to classify cells in the mouse somatosensory cortex and hippocampal CA1 region and found 47 molecularly distinct subclasses, comprising all known major cell types in the cortex.
Journal ArticleDOI
Fate Mapping Reveals Origins and Dynamics of Monocytes and Tissue Macrophages under Homeostasis
Simon Yona,Ki-Wook Kim,Yochai Wolf,Alexander Mildner,Diana Varol,Michal Breker,Dalit Strauss-Ayali,Sergey Viukov,Martin Guilliams,Alexander V. Misharin,David A. Hume,Harris Perlman,Bernard Malissen,Elazar Zelzer,Steffen Jung +14 more
TL;DR: A fate-mapping study of the murine monocyte and macrophage compartment taking advantage of constitutive and conditional CX(3)CR1 promoter-driven Cre recombinase expression is reported, establishing that short-lived Ly6C(+) monocytes constitute obligatory steady-state precursors of blood-resident Ly 6C(-) cells and that the abundance of Ly6 C(+) blood monocytes dynamically controls the circulation lifespan of their progeny.
Journal ArticleDOI
Host microbiota constantly control maturation and function of microglia in the CNS
Daniel Erny,Anna Lena Hrabě de Angelis,Diego Jaitin,Peter Wieghofer,Ori Staszewski,Eyal David,Hadas Keren-Shaul,Tanel Mahlakõiv,Kristin Jakobshagen,Thorsten Buch,Vera Schwierzeck,Olaf Utermöhlen,Eunyoung Chun,Wendy S. Garrett,Kathy D. McCoy,Andreas Diefenbach,Peter Staeheli,Bärbel Stecher,Ido Amit,Marco Prinz +19 more
TL;DR: It is determined that short-chain fatty acids (SCFA), microbiota-derived bacterial fermentation products, regulated microglia homeostasis and mice deficient for the SCFA receptor FFAR2 mirroredmicroglia defects found under GF conditions, suggesting that host bacteria vitally regulate microglian maturation and function.
Journal ArticleDOI
A Lineage of Myeloid Cells Independent of Myb and Hematopoietic Stem Cells
Christian Schulz,Elisa Gomez Perdiguero,Laurent Chorro,Heather L. Szabo-Rogers,Nicolas Cagnard,Katrin Kierdorf,Marco Prinz,Bishan Wu,Sten Eirik W. Jacobsen,Jeffrey W. Pollard,Jon Frampton,Karen J. Liu,Frederic Geissmann +12 more
TL;DR: It is found that the transcription factor Myb was required for development of HSCs and all CD11bhigh monocytes and macrophages, but was dispensable for yolk sac (YS)macrophages and for the development of YS-derived F4/80bright macrophage populations in several tissues.