Journal ArticleDOI
Ontogeny and homeostasis of CNS myeloid cells.
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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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CYBB/NOX2 in conventional DCs controls T cell encephalitogenicity during neuroinflammation
Christian W. Keller,Christian W. Keller,Monika B. Kotur,Sarah Mundt,Nikolaos Dokalis,Laure-Anne Ligeon,Ajay M. Shah,Marco Prinz,Burkhard Becher,Christian Münz,Jan D. Lünemann,Jan D. Lünemann +11 more
TL;DR: Genetic ablation of Cybb in cDCs is sufficient to restrain encephalitogenic TH cell recruitment into the CNS and to ameliorate clinical disease development upon the adoptive transfer of MOG-specific CD4+ T cells.
Journal ArticleDOI
The Human Endolymphatic Sac and Inner Ear Immunity: Macrophage Interaction and Molecular Expression
Charlotta Kämpfe Nordström,Niklas Danckwardt-Lillieström,Göran Laurell,Wei Liu,Helge Rask-Andersen +4 more
TL;DR: High-resolution immunohistochemistry shows that antigens reaching the ear may be trapped and processed by an immune cell machinery located in the ES, thereby inflammatory activity may be evaded near the vulnerable inner ear sensory structures.
Journal ArticleDOI
The Early Innate Immune Response to, and Phagocyte-Dependent Entry of, Cryptococcus neoformans Map to the Perivascular Space of Cortical Post-Capillary Venules in Neurocryptococcosis
Keren Kaufman-Francis,Julianne T. Djordjevic,Pierre-Georges Juillard,Sophie Lev,Desmarini Desmarini,Georges E. Grau,Tania C. Sorrell +6 more
TL;DR: It is demonstrated for the first time that the PVS of cortical post-capillary venules is the major site of the early innate immune response to, and phagocyte-dependent entry of, C. neoformans.
Journal ArticleDOI
Loss of homeostatic microglial phenotype in CSF1R- related Leukoencephalopathy
Liam Kempthorne,Liam Kempthorne,Hyejin Yoon,Charlotte Madore,Scott T. Smith,Zbigniew K. Wszolek,Rosa Rademakers,Jungsu Kim,Oleg Butovsky,Dennis W. Dickson +9 more
TL;DR: The findings suggest a potential mechanism of disease pathogenesis by linking aberrant CSF-1 signaling to altered microglial phenotype and support the idea that HDLS may be a primary microgliopathy.
Journal ArticleDOI
Regulatory function of microRNAs in microglia.
TL;DR: In this review, recent findings on the role of miRNAs as drivers of microglia phenotypic changes and their cotribution in neurological disease are addressed.
References
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Journal ArticleDOI
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.
Journal ArticleDOI
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.