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Gut-educated IgA plasma cells defend the meningeal venous sinuses.
Fitzpatrick, Zachary; Frazer, Gordon; Ferro, Ashley; Clare, Simon; Bouladoux, Nicolas; Ferdinand, John; Tuong, Zewen Kelvin; Negro-Demontel, Maria Luciana; Kumar, Nitin; Suchanek, Ondrej; Tajsic, Tamara; Harcourt, Katherine; Scott, Kirsten; Bashford-Rogers, Rachel; Helmy, Adel; Reich, Daniel S; Belkaid, Yasmine; Lawley, Trevor D; McGavern, Dorian B; Clatworthy, Menna R.
Afiliación
  • Fitzpatrick Z; Molecular Immunity Unit, Department of Medicine, University of Cambridge, Cambridge, UK.
  • Frazer G; Viral Immunology and Intravital Imaging Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MA, USA.
  • Ferro A; Molecular Immunity Unit, Department of Medicine, University of Cambridge, Cambridge, UK.
  • Clare S; Molecular Immunity Unit, Department of Medicine, University of Cambridge, Cambridge, UK.
  • Bouladoux N; Host-Microbiota Interactions Laboratory, Wellcome Sanger Institute, Hinxton, UK.
  • Ferdinand J; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MA, USA.
  • Tuong ZK; Molecular Immunity Unit, Department of Medicine, University of Cambridge, Cambridge, UK.
  • Negro-Demontel ML; Molecular Immunity Unit, Department of Medicine, University of Cambridge, Cambridge, UK.
  • Kumar N; Cellular Genetics, Wellcome Sanger Institute, Hinxton, UK.
  • Suchanek O; Viral Immunology and Intravital Imaging Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MA, USA.
  • Tajsic T; Host-Microbiota Interactions Laboratory, Wellcome Sanger Institute, Hinxton, UK.
  • Harcourt K; Molecular Immunity Unit, Department of Medicine, University of Cambridge, Cambridge, UK.
  • Scott K; Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
  • Bashford-Rogers R; Host-Microbiota Interactions Laboratory, Wellcome Sanger Institute, Hinxton, UK.
  • Helmy A; Molecular Immunity Unit, Department of Medicine, University of Cambridge, Cambridge, UK.
  • Reich DS; John van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
  • Belkaid Y; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
  • Lawley TD; Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
  • McGavern DB; Translational Neuroradiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MA, USA.
  • Clatworthy MR; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MA, USA.
Nature ; 587(7834): 472-476, 2020 11.
Article en En | MEDLINE | ID: mdl-33149302
The central nervous system has historically been viewed as an immune-privileged site, but recent data have shown that the meninges-the membranes that surround the brain and spinal cord-contain a diverse population of immune cells1. So far, studies have focused on macrophages and T cells, but have not included a detailed analysis of meningeal humoral immunity. Here we show that, during homeostasis, the mouse and human meninges contain IgA-secreting plasma cells. These cells are positioned adjacent to dural venous sinuses: regions of slow blood flow with fenestrations that can potentially permit blood-borne pathogens to access the brain2. Peri-sinus IgA plasma cells increased with age and following a breach of the intestinal barrier. Conversely, they were scarce in germ-free mice, but their presence was restored by gut re-colonization. B cell receptor sequencing confirmed that meningeal IgA+ cells originated in the intestine. Specific depletion of meningeal plasma cells or IgA deficiency resulted in reduced fungal entrapment in the peri-sinus region and increased spread into the brain following intravenous challenge, showing that meningeal IgA is essential for defending the central nervous system at this vulnerable venous barrier surface.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Plasmáticas / Inmunoglobulina A Secretora / Senos Craneales / Microbioma Gastrointestinal / Intestinos / Meninges Límite: Aged / Animals / Female / Humans / Male Idioma: En Revista: Nature Año: 2020 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Plasmáticas / Inmunoglobulina A Secretora / Senos Craneales / Microbioma Gastrointestinal / Intestinos / Meninges Límite: Aged / Animals / Female / Humans / Male Idioma: En Revista: Nature Año: 2020 Tipo del documento: Article Pais de publicación: Reino Unido