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Science (New York, N.Y.) Apr 2023Contemporary studies have completely changed the view of brain immunity from envisioning the brain as isolated and inaccessible to peripheral immune cells to an organ in... (Review)
Review
Contemporary studies have completely changed the view of brain immunity from envisioning the brain as isolated and inaccessible to peripheral immune cells to an organ in close physical and functional communication with the immune system for its maintenance, function, and repair. Circulating immune cells reside in special niches in the brain's borders, the choroid plexus, meninges, and perivascular spaces, from which they patrol and sense the brain in a remote manner. These niches, together with the meningeal lymphatic system and skull microchannels, provide multiple routes of interaction between the brain and the immune system, in addition to the blood vasculature. In this Review, we describe current ideas about brain immunity and their implications for brain aging, diseases, and immune-based therapeutic approaches.
Topics: Animals; Humans; Brain; Cell Movement; Immune System; Lymphatic System; Meninges; Myeloid Cells
PubMed: 37023203
DOI: 10.1126/science.abo7649 -
Archives of Virology Feb 2021Meningitis is a serious condition that affects the central nervous system. It is an inflammation of the meninges, which is the membrane that surrounds both the brain and... (Review)
Review
Meningitis is a serious condition that affects the central nervous system. It is an inflammation of the meninges, which is the membrane that surrounds both the brain and the spinal cord. Meningitis can be caused by bacterial, viral, or fungal infections. Many viruses, such as enteroviruses, herpesviruses, and influenza viruses, can cause this neurological disorder. However, enteroviruses have been found to be the underlying cause of most viral meningitis cases worldwide. With few exceptions, the clinical manifestations and symptoms associated with viral meningitis are similar for the different causative agents, which makes it difficult to diagnose the disease at early stages. The pathogenesis of viral meningitis is not clearly defined, and more studies are needed to improve the health care of patients in terms of early diagnosis and management. This review article discusses the most common causative agents, epidemiology, clinical features, diagnosis, and pathogenesis of viral meningitis.
Topics: Animals; Humans; Meningitis, Viral; Viruses
PubMed: 33392820
DOI: 10.1007/s00705-020-04891-1 -
Neurologic Clinics Feb 2022Meningitis and encephalitis are inflammatory syndromes of the meninges and brain parenchyma, respectively, and may be identified either by finding definitive evidence of... (Review)
Review
Meningitis and encephalitis are inflammatory syndromes of the meninges and brain parenchyma, respectively, and may be identified either by finding definitive evidence of inflammation on tissue pathology or by cerebrocpinal fluid (CSF) analysis showing pleocytosis or intrathecal antibody synthesis. Clinicians evaluating undifferentiated meningitis or encephalitis should simultaneously consider autoimmune, infectious, and neoplastic causes, using patient risk factors, clinical syndrome, and diagnostic results including CSF and MRI findings to narrow the differential diagnosis. If an autoimmune cause is favored, an important early diagnostic question is whether a specific neural autoantibody is likely to be identified.
Topics: Autoantibodies; Brain; Encephalitis; Humans; Magnetic Resonance Imaging; Meningitis
PubMed: 34798977
DOI: 10.1016/j.ncl.2021.08.007 -
Nature Mar 2023The meninges are densely innervated by nociceptive sensory neurons that mediate pain and headache. Bacterial meningitis causes life-threatening infections of the...
The meninges are densely innervated by nociceptive sensory neurons that mediate pain and headache. Bacterial meningitis causes life-threatening infections of the meninges and central nervous system, affecting more than 2.5 million people a year. How pain and neuroimmune interactions impact meningeal antibacterial host defences are unclear. Here we show that Nav1.8 nociceptors signal to immune cells in the meninges through the neuropeptide calcitonin gene-related peptide (CGRP) during infection. This neuroimmune axis inhibits host defences and exacerbates bacterial meningitis. Nociceptor neuron ablation reduced meningeal and brain invasion by two bacterial pathogens: Streptococcus pneumoniae and Streptococcus agalactiae. S. pneumoniae activated nociceptors through its pore-forming toxin pneumolysin to release CGRP from nerve terminals. CGRP acted through receptor activity modifying protein 1 (RAMP1) on meningeal macrophages to polarize their transcriptional responses, suppressing macrophage chemokine expression, neutrophil recruitment and dural antimicrobial defences. Macrophage-specific RAMP1 deficiency or pharmacological blockade of RAMP1 enhanced immune responses and bacterial clearance in the meninges and brain. Therefore, bacteria hijack CGRP-RAMP1 signalling in meningeal macrophages to facilitate brain invasion. Targeting this neuroimmune axis in the meninges can enhance host defences and potentially produce treatments for bacterial meningitis.
Topics: Humans; Brain; Calcitonin Gene-Related Peptide; Meninges; Neuroimmunomodulation; Pain; NAV1.8 Voltage-Gated Sodium Channel; Meningitis, Bacterial; Streptococcus agalactiae; Streptococcus pneumoniae; Nociceptors; Receptor Activity-Modifying Protein 1; Macrophages
PubMed: 36859544
DOI: 10.1038/s41586-023-05753-x -
Immunity Nov 2022The surface of the central nervous system (CNS) is protected by the meninges, which contain a dense network of meningeal macrophages (MMs). Here, we examined the role of...
The surface of the central nervous system (CNS) is protected by the meninges, which contain a dense network of meningeal macrophages (MMs). Here, we examined the role of tissue-resident MM in viral infection. MHC-II MM were abundant neonatally, whereas MHC-II MM appeared over time. These barrier macrophages differentially responded to in vivo peripheral challenges such as LPS, SARS-CoV-2, and lymphocytic choriomeningitis virus (LCMV). Peripheral LCMV infection, which was asymptomatic, led to a transient infection and activation of the meninges. Mice lacking macrophages but conserving brain microglia, or mice bearing macrophage-specific deletion of Stat1 or Ifnar, exhibited extensive viral spread into the CNS. Transcranial pharmacological depletion strategies targeting MM locally resulted in several areas of the meninges becoming infected and fatal meningitis. Low numbers of MHC-II MM, which is seen upon LPS challenge or in neonates, corelated with higher viral load upon infection. Thus, MMs protect against viral infection and may present targets for therapeutic manipulation.
Topics: Animals; Mice; Lipopolysaccharides; Mice, Inbred C57BL; SARS-CoV-2; COVID-19; Lymphocytic Choriomeningitis; Lymphocytic choriomeningitis virus; Macrophages; Meninges
PubMed: 36323311
DOI: 10.1016/j.immuni.2022.10.005 -
Science (New York, N.Y.) Jul 2021The meninges are a membranous structure enveloping the central nervous system (CNS) that host a rich repertoire of immune cells mediating CNS immune surveillance. Here,...
The meninges are a membranous structure enveloping the central nervous system (CNS) that host a rich repertoire of immune cells mediating CNS immune surveillance. Here, we report that the mouse meninges contain a pool of monocytes and neutrophils supplied not from the blood but by adjacent skull and vertebral bone marrow. Under pathological conditions, including spinal cord injury and neuroinflammation, CNS-infiltrating myeloid cells can originate from brain borders and display transcriptional signatures distinct from their blood-derived counterparts. Thus, CNS borders are populated by myeloid cells from adjacent bone marrow niches, strategically placed to supply innate immune cells under homeostatic and pathological conditions. These findings call for a reinterpretation of immune-cell infiltration into the CNS during injury and autoimmunity and may inform future therapeutic approaches that harness meningeal immune cells.
Topics: Animals; Bone Marrow; Bone Marrow Cells; Brain; Cell Movement; Central Nervous System; Central Nervous System Diseases; Dura Mater; Encephalomyelitis, Autoimmune, Experimental; Homeostasis; Meninges; Mice; Monocytes; Myeloid Cells; Neutrophils; Skull; Spinal Cord; Spinal Cord Injuries; Spine
PubMed: 34083447
DOI: 10.1126/science.abf7844 -
Science (New York, N.Y.) Jan 2023The central nervous system is lined by meninges, classically known as dura, arachnoid, and pia mater. We show the existence of a fourth meningeal layer that...
The central nervous system is lined by meninges, classically known as dura, arachnoid, and pia mater. We show the existence of a fourth meningeal layer that compartmentalizes the subarachnoid space in the mouse and human brain, designated the subarachnoid lymphatic-like membrane (SLYM). SLYM is morpho- and immunophenotypically similar to the mesothelial membrane lining of peripheral organs and body cavities, and it encases blood vessels and harbors immune cells. Functionally, the close apposition of SLYM with the endothelial lining of the meningeal venous sinus permits direct exchange of small solutes between cerebrospinal fluid and venous blood, thus representing the mouse equivalent of the arachnoid granulations. The functional characterization of SLYM provides fundamental insights into brain immune barriers and fluid transport.
Topics: Animals; Humans; Mice; Dura Mater; Endothelium; Subarachnoid Space; Epithelium; Brain; Cerebrospinal Fluid
PubMed: 36603070
DOI: 10.1126/science.adc8810 -
Continuum (Minneapolis, Minn.) Aug 2021This article reviews the diagnosis and treatment of infectious meningitis, including updates on newer molecular diagnostic techniques for microbiological diagnosis. (Review)
Review
PURPOSE OF REVIEW
This article reviews the diagnosis and treatment of infectious meningitis, including updates on newer molecular diagnostic techniques for microbiological diagnosis.
RECENT FINDINGS
New polymerase chain reaction (PCR)-based molecular diagnostic techniques have improved the timeliness of microbiological diagnosis in meningitis, but clinicians must be aware of the limitations of such tests. Next-generation sequencing can now be applied to CSF, allowing for diagnosis of infections not identifiable by conventional means.
SUMMARY
Infectious meningitis can be caused by a broad range of organisms. The clinician must be aware of the test characteristics of new molecular techniques for microbiological diagnosis as well as traditional techniques to tailor antimicrobial therapy appropriately in patients with meningitis.
Topics: Humans; Meningitis; Polymerase Chain Reaction
PubMed: 34623095
DOI: 10.1212/CON.0000000000001016 -
Revue Neurologique 2019Aseptic meningitis is defined as meningeal inflammation - i.e. cerebrospinal fluid (CSF) pleocytosis≥5 cells/mm - not related to an infectious process. Etiologies... (Review)
Review
Aseptic meningitis is defined as meningeal inflammation - i.e. cerebrospinal fluid (CSF) pleocytosis≥5 cells/mm - not related to an infectious process. Etiologies of aseptic meningitis can be classified in three main groups: (i) systemic diseases with meningeal involvement, which include sarcoidosis, Behçet's disease, Sjögren's syndrome, systemic lupus erythematosus and granulomatosis with polyangiitis; (ii) drug-induced aseptic meningitis, mostly reported with non-steroidal anti-inflammatory drugs (NSAIDs), antibiotics (sulfamides, penicillins), intravenous immunoglobulin, and monoclonal antibodies; (iii) neoplastic meningitis, either related to solid cancer metastasis (breast cancer, lung cancer, melanoma) or malignant hemopathy (lymphoma, leukemia). Most series in the literature included groups of meningitis that are not stricto sensu aseptic, but should rather be included in the differential diagnosis: (i) infectious meningitis related to virus, parasites, fungi, or fastidious bacteria that require specific diagnostic investigations; (ii) bacterial meningitis with sterile CSF due to previous antibiotic administration, and (iii) parameningeal infections associated with meningeal reaction. Despite progress in microbiological diagnosis (including PCR, and next generation sequencing), and identification of a growing panel of autoimmune or paraneoplastic neurological syndromes, up to two thirds of aseptic meningitis cases are of unknown etiology, finally labeled as 'idiopathic'. Description of new entities, such as the syndrome of transient headache and neurologic deficits with cerebrospinal fluid lymphocytosis (HaNDL) may decrease the proportion of idiopathic aseptic meningitis. This state-of-the-art review summarizes the characteristics of main causes of aseptic meningitis.
Topics: Humans; Meningitis, Aseptic
PubMed: 31375286
DOI: 10.1016/j.neurol.2019.07.005 -
The New England Journal of Medicine Sep 2021
Review
Topics: Cerebrospinal Fluid; Chronic Disease; Diagnosis, Differential; Humans; Magnetic Resonance Imaging; Meningitis; Polymerase Chain Reaction; Prognosis; Spinal Puncture
PubMed: 34469648
DOI: 10.1056/NEJMra2032996