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Journal of Immunology (Baltimore, Md. :... Jan 2020At steady state, the CNS parenchyma has few to no lymphocytes and less potent Ag-presentation capability compared with other organs. However, the meninges surrounding... (Review)
Review
At steady state, the CNS parenchyma has few to no lymphocytes and less potent Ag-presentation capability compared with other organs. However, the meninges surrounding the CNS host diverse populations of immune cells that influence how CNS-related immune responses develop. Interstitial and cerebrospinal fluid produced in the CNS is continuously drained, and recent advances have emphasized that this process is largely taking place through the lymphatic system. To what extent this fluid process mobilizes CNS-derived Ags toward meningeal immune cells and subsequently the peripheral immune system through the lymphatic vessel network is a question of significant clinical importance for autoimmunity, tumor immunology, and infectious disease. Recent advances in understanding the role of meningeal lymphatics as a communicator between the brain and peripheral immunity are discussed in this review.
Topics: Animals; Brain; Central Nervous System; Humans; Immunologic Surveillance; Lymphatic Vessels; Meninges
PubMed: 31907271
DOI: 10.4049/jimmunol.1900838 -
Frontiers in Immunology 2024
Topics: Humans; Tuberculosis, Meningeal; Mycobacterium tuberculosis; Antitubercular Agents; Disease Management
PubMed: 38933279
DOI: 10.3389/fimmu.2024.1433345 -
Proceedings of the National Academy of... Sep 2021Ectopic lymphoid tissue containing B cells forms in the meninges at late stages of human multiple sclerosis (MS) and when neuroinflammation is induced by interleukin...
Ectopic lymphoid tissue containing B cells forms in the meninges at late stages of human multiple sclerosis (MS) and when neuroinflammation is induced by interleukin (IL)-17 producing T helper (Th17) cells in rodents. B cell differentiation and the subsequent release of class-switched immunoglobulins have been speculated to occur in the meninges, but the exact cellular composition and underlying mechanisms of meningeal-dominated inflammation remain unknown. Here, we performed in-depth characterization of meningeal versus parenchymal Th17-induced rodent neuroinflammation. The most pronounced cellular and transcriptional differences between these compartments was the localization of B cells exhibiting a follicular phenotype exclusively to the meninges. Correspondingly, meningeal but not parenchymal Th17 cells acquired a B cell-supporting phenotype and resided in close contact with B cells. This preferential B cell tropism for the meninges and the formation of meningeal ectopic lymphoid tissue was partially dependent on the expression of the transcription factor Bcl6 in Th17 cells that is required in other T cell lineages to induce isotype class switching in B cells. A function of Bcl6 in Th17 cells was only detected in vivo and was reflected by the induction of B cell-supporting cytokines, the appearance of follicular B cells in the meninges, and of immunoglobulin class switching in the cerebrospinal fluid. We thus identify the induction of a B cell-supporting meningeal microenvironment by Bcl6 in Th17 cells as a mechanism controlling compartment specificity in neuroinflammation.
Topics: Animals; B-Lymphocytes; Cell Communication; Cytokines; Encephalomyelitis, Autoimmune, Experimental; Female; Germinal Center; Inflammation; Lymphocyte Activation; Male; Meninges; Mice; Mice, Inbred C57BL; Multiple Sclerosis; Neuroinflammatory Diseases; Parenchymal Tissue; Proto-Oncogene Proteins c-bcl-6; Th17 Cells
PubMed: 34479995
DOI: 10.1073/pnas.2023174118 -
Neuroimaging Clinics of North America Feb 2023Neuroimaging provides rapid, noninvasive visualization of central nervous system infections for optimal diagnosis and management. Generalizable and characteristic... (Review)
Review
Neuroimaging provides rapid, noninvasive visualization of central nervous system infections for optimal diagnosis and management. Generalizable and characteristic imaging patterns help radiologists distinguish different types of intracranial infections including meningitis and cerebritis from a variety of bacterial, viral, fungal, and/or parasitic causes. Here, we describe key radiologic patterns of meningeal enhancement and diffusion restriction through profiles of meningitis, cerebritis, abscess, and ventriculitis. We discuss various imaging modalities and recent diagnostic advances such as deep learning through a survey of intracranial pathogens and their radiographic findings. Moreover, we explore critical complications and differential diagnoses of intracranial infections.
Topics: Humans; Neuroimaging; Meningitis; Diagnosis, Differential
PubMed: 36404039
DOI: 10.1016/j.nic.2022.07.001 -
Emerging Microbes & Infections Aug 2017Cases of tuberculosis/cryptococcosis co-infection are rapidly increasing in China. However, most studies addressing this co-infection have been published in Chinese... (Review)
Review
Cases of tuberculosis/cryptococcosis co-infection are rapidly increasing in China. However, most studies addressing this co-infection have been published in Chinese journals, and this publication strategy has obscured this disease trend for scientists in other parts of the world. Our investigation found that 62.9% of all co-infection cases worldwide were reported in the Chinese population (n=197) between 1965 and 2016, and 56.3% of these Chinese cases were reported after 2010. Nearly all cases originated from the warm and wet monsoon regions of China. HIV-positive subjects tended to correlate with more severe manifestations of a tuberculosis/cryptococcosis co-infection than those without HIV. Notablely, dual tubercular/cryptococcal meningitis was the most frequent (54.0%) and most easily misdiagnosed (95.2%, n=40/42) co-infection. We also found that the combined use of cerebrospinal fluid pressure and concentrations of glucose, protein and chlorine might be an inexpensive and effective indicator to differentiate tubercular/cryptococcal co-infection meningitis from tubercular meningitis and cryptococcal meningitis.
Topics: Adult; Cerebrospinal Fluid Proteins; China; Chlorine; Coinfection; Cryptococcosis; Diagnostic Errors; Female; Glucose; HIV Infections; Hospitalization; Humans; Male; Meningitis, Cryptococcal; Retrospective Studies; Tuberculosis; Tuberculosis, Meningeal
PubMed: 28831193
DOI: 10.1038/emi.2017.61 -
Journal of Clinical Microbiology May 2016Meningitis and encephalitis are potentially life-threatening diseases with a wide array of infectious, postinfectious, and noninfectious causes. Diagnostic testing is... (Review)
Review
Meningitis and encephalitis are potentially life-threatening diseases with a wide array of infectious, postinfectious, and noninfectious causes. Diagnostic testing is central to determining the underlying etiology, treatment, and prognosis, but many patients remain undiagnosed due to suboptimal testing and lack of tests for all pathogens. In this article, we summarize the epidemiology, barriers to diagnosis, and current best tests for meningitis and encephalitis in developed countries. We end with a brief discussion of new test methods, such as multiplex panel-based tests and metagenomic sequencing, which are likely to alter diagnostic strategies for these conditions in the near future.
Topics: Community-Acquired Infections; Diagnostic Tests, Routine; Encephalitis; Humans; Meningitis; Microbiological Techniques
PubMed: 26888896
DOI: 10.1128/JCM.00289-16 -
Stroke Jul 2021Fibroblasts are the most common cell type of connective tissues. In the central nervous system (CNS), fibroblast-like cells are mainly located in the meninges and... (Review)
Review
Fibroblasts are the most common cell type of connective tissues. In the central nervous system (CNS), fibroblast-like cells are mainly located in the meninges and perivascular Virchow-Robin space. The origins of these fibroblast-like cells and their functions in both CNS development and pathological conditions remain largely unknown. In this review, we first introduce the anatomic location and molecular markers of CNS fibroblast-like cells. Next, the functions of fibroblast-like cells in CNS development and neurological disorders, including stroke, CNS traumatic injuries, and other neurological diseases, are discussed. Third, current challenges and future directions in the field are summarized. We hope to provide a synthetic review that stimulates future research on CNS fibroblast-like cells.
Topics: Animals; Central Nervous System; Fibroblasts; Humans; Meninges; Nervous System Diseases; Stroke
PubMed: 33940953
DOI: 10.1161/STROKEAHA.120.033431 -
Cancer Control : Journal of the Moffitt... Jan 2017Neoplastic meningitis is a complication of solid and hematological malignancies. It consists of the spread of malignant cells to the leptomeninges and subarachnoid space... (Review)
Review
BACKGROUND
Neoplastic meningitis is a complication of solid and hematological malignancies. It consists of the spread of malignant cells to the leptomeninges and subarachnoid space and their dissemination within the cerebrospinal fluid.
METHODS
A literature review was conducted to summarize the clinical presentation, differential diagnosis, laboratory values, and imaging findings of neoplastic meningitis.
RESULTS
Neoplastic meningitis is an event in the course of cancer with a variable clinical presentation and a wide differential diagnosis. In general, characteristic findings on gadolinium-enhanced magnetic resonance imaging and the presence of malignant cells in the cerebrospinal fluid remain the cornerstones of diagnosis. However, both modalities do not always confirm the diagnosis of neoplastic meningitis despite a typical clinical picture.
CONCLUSIONS
Clinicians treating patients with cancer should be aware of the possibility of neoplastic meningitis, especially when multilevel neurological symptoms are present. Neoplastic meningitis can be an elusive diagnosis, so clinician awareness is important so that this malignant manifestation is recognized in a timely manner.
Topics: Diagnosis, Differential; Diagnostic Imaging; Humans; Meningeal Neoplasms; Meningitis; Severity of Illness Index
PubMed: 28178708
DOI: 10.1177/107327481702400103 -
Annals of Neurology Apr 2018Gray matter (GM) damage and meningeal inflammation have been associated with early disease onset and a more aggressive disease course in multiple sclerosis (MS), but can...
OBJECTIVE
Gray matter (GM) damage and meningeal inflammation have been associated with early disease onset and a more aggressive disease course in multiple sclerosis (MS), but can these changes be identified in the patient early in the disease course?
METHODS
To identify possible biomarkers linking meningeal inflammation, GM damage, and disease severity, gene and protein expression were analyzed in meninges and cerebrospinal fluid (CSF) from 27 postmortem secondary progressive MS and 14 control cases. Combined cytokine/chemokine CSF profiling and 3T magnetic resonance imaging (MRI) were performed at diagnosis in 2 independent cohorts of MS patients (35 and 38 subjects) and in 26 non-MS patients.
RESULTS
Increased expression of proinflammatory cytokines (IFNγ, TNF, IL2, and IL22) and molecules related to sustained B-cell activity and lymphoid-neogenesis (CXCL13, CXCL10, LTα, IL6, and IL10) was detected in the meninges and CSF of postmortem MS cases with high levels of meningeal inflammation and GM demyelination. Similar proinflammatory patterns, including increased levels of CXCL13, TNF, IFNγ, CXCL12, IL6, IL8, and IL10, together with high levels of BAFF, APRIL, LIGHT, TWEAK, sTNFR1, sCD163, MMP2, and pentraxin III, were detected in the CSF of MS patients with higher levels of GM damage at diagnosis.
INTERPRETATION
A common pattern of intrathecal (meninges and CSF) inflammatory profile strongly correlates with increased cortical pathology, both at the time of diagnosis and at death. These results suggest a role for detailed CSF analysis combined with MRI as a prognostic marker for more aggressive MS. Ann Neurol 2018 Ann Neurol 2018;83:739-755.
Topics: Adult; Aged; Aged, 80 and over; Autopsy; Cerebral Cortex; Cohort Studies; Cytokines; Disease Progression; Female; Gray Matter; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Meninges; Middle Aged; Multiple Sclerosis; ROC Curve
PubMed: 29518260
DOI: 10.1002/ana.25197 -
Glymphatic-lymphatic coupling: assessment of the evidence from magnetic resonance imaging of humans.Cellular and Molecular Life Sciences :... Mar 2024The discoveries that cerebrospinal fluid participates in metabolic perivascular exchange with the brain and further drains solutes to meningeal lymphatic vessels have... (Review)
Review
The discoveries that cerebrospinal fluid participates in metabolic perivascular exchange with the brain and further drains solutes to meningeal lymphatic vessels have sparked a tremendous interest in translating these seminal findings from animals to humans. A potential two-way coupling between the brain extra-vascular compartment and the peripheral immune system has implications that exceed those concerning neurodegenerative diseases, but also imply that the central nervous system has pushed its immunological borders toward the periphery, where cross-talk mediated by cerebrospinal fluid may play a role in a range of neoplastic and immunological diseases. Due to its non-invasive approach, magnetic resonance imaging has typically been the preferred methodology in attempts to image the glymphatic system and meningeal lymphatics in humans. Even if flourishing, the research field is still in its cradle, and interpretations of imaging findings that topographically associate with reports from animals have yet seemed to downplay the presence of previously described anatomical constituents, particularly in the dura. In this brief review, we illuminate these challenges and assess the evidence for a glymphatic-lymphatic coupling. Finally, we provide a new perspective on how human brain and meningeal clearance function may possibly be measured in future.
Topics: Animals; Humans; Lymphatic Vessels; Central Nervous System; Brain; Meninges; Magnetic Resonance Imaging
PubMed: 38472405
DOI: 10.1007/s00018-024-05141-2