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
Citations
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CARD9+ microglia promote antifungal immunity via IL-1β- and CXCL1-mediated neutrophil recruitment
Rebecca A. Drummond,Rebecca A. Drummond,Muthulekha Swamydas,Vasileios Oikonomou,Bing Zhai,Ivy M. Dambuza,Brian C. Schaefer,Andrea C. Bohrer,Katrin D. Mayer-Barber,Sergio A. Lira,Yoichir Iwakura,Scott G. Filler,Gordon D. Brown,Bernhard Hube,Bernhard Hube,Julian R. Naglik,Tobias M. Hohl,Michail S. Lionakis +17 more
TL;DR: Candidalysin is identified, a Candida virulence factor that elicits microglial expression of the cytokine IL-1β and chemokine CXCL1 and facilitates neutrophil recruitment and alteration of this pathway impairs antifungal responses.
Journal ArticleDOI
Brain perivascular macrophages: characterization and functional roles in health and disease.
TL;DR: The available evidence supports the idea that PVM are a key component of the brain-resident immune system with broad implications for the pathogenesis of major brain diseases.
Journal ArticleDOI
The Role of Microglia and Macrophages in CNS Homeostasis, Autoimmunity, and Cancer
TL;DR: Given the essential role of CNS microglia and macrophages in the regulation of all types of CNS disorders, agents targeting these subsets are currently applied in preclinical and clinical trials, it is believed that a better understanding of the biology of these macrophage subsets offers new exciting paths for therapeutic intervention.
Journal ArticleDOI
A20 critically controls microglia activation and inhibits inflammasome-dependent neuroinflammation
Sofie Voet,Conor Mc Guire,Nora Hagemeyer,Arne Martens,Anna Schroeder,Peter Wieghofer,Peter Wieghofer,Carmen Daems,Ori Staszewski,Lieselotte Vande Walle,Marta Joana Costa Jordão,Mozes Sze,Hanna-Kaisa Vikkula,Delphine Demeestere,Griet Van Imschoot,Charlotte L. Scott,Esther Hoste,Amanda Gonçalves,Martin Guilliams,Saskia Lippens,Claude Libert,Roosmarijn E. Vandenbroucke,Ki-Wook Kim,Ki-Wook Kim,Steffen Jung,Zsuzsanna Callaerts-Vegh,Patrick Callaerts,Joris de Wit,Mohamed Lamkanfi,Marco Prinz,Geert van Loo +30 more
TL;DR: It is demonstrated that the nuclear factor kappa B (NF-κB) regulatory protein A20 is crucial in regulating microglia activation during CNS homeostasis and pathology and exacerbates multiple sclerosis-like disease.
Journal ArticleDOI
Profiling peripheral nerve macrophages reveals two macrophage subsets with distinct localization, transcriptome and response to injury.
Elke Ydens,Lukas Amann,Bob Asselbergh,Charlotte L. Scott,Charlotte L. Scott,Liesbet Martens,Dorine Sichien,Omar Mossad,Thomas Blank,Sofie De Prijck,Donovan Low,Takahiro Masuda,Yvan Saeys,Vincent Timmerman,Ralf Stumm,Florent Ginhoux,Marco Prinz,Sophie Janssens,Martin Guilliams +18 more
TL;DR: It is shown that sciatic nerve macrophage populations do not derive from the early embryonic precursors colonizing the CNS, but originate primarily from late embryonic precursor and become replaced by bone-marrow-derived macrophages over time.
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.