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Bacterial peptidoglycan and immune reactivity in the central nervous system in multiple sclerosis
I A Schrijver1, M van Meurs, M J Melief
1Departments of Immunology and Neurology, Erasmus University and University Hospital Rotterdam-Dijkzigt, Rotterdam and Netherlands Brain Bank, Amsterdam, The Netherlands.
Abstract:
Multiple sclerosis is believed to result from a CD4+ T-cell response against myelin antigens. Peptidoglycan, a major component of the Gram-positive bacterial cell wall, is a functional lipopolysaccharide analogue with potent proinflammatory properties and is conceivably a mediator of sterile inflammation. Here we demonstrate that peptidoglycan is present within antigen-presenting cells in the brain of multiple sclerosis patients. These cells have macrophage and dendritic cell characteristics, and are immunocompetent as evidenced by co-expression of inflammatory cytokines and co-stimulatory molecules. In addition, intrathecal plasma cells specific for peptidoglycan are present in multiple sclerosis brain tissue, and antibodies binding peptidoglycan are present in CSF during active disease. Peptidoglycan may thus contribute to T- and B-cell activity during brain inflammation without a requirement for local bacterial replication.
Insights
Peptidoglycan, a bacterial molecule, was found in the brains of multiple sclerosis patients, suggesting it may drive autoimmune responses and brain inflammation without local bacterial infection.
Area of Science:
- Neuroimmunology
- Microbial Immunology
Background:
- Multiple sclerosis (MS) is an autoimmune disease involving CD4+ T-cell responses to myelin antigens.
- Peptidoglycan (PG) is a bacterial cell wall component with pro-inflammatory properties, potentially mediating sterile inflammation.
Purpose of the Study:
- To investigate the presence and role of peptidoglycan in the brain during multiple sclerosis.
Main Methods:
- Immunohistochemistry to detect peptidoglycan in brain tissue.
- Analysis of antigen-presenting cells (APCs) for inflammatory markers.
- Detection of PG-specific plasma cells and antibodies in cerebrospinal fluid (CSF).
Main Results:
- Peptidoglycan was detected within APCs (macrophages, dendritic cells) in the brains of MS patients.
- These APCs expressed inflammatory cytokines and co-stimulatory molecules, indicating immune activation.
- Intrathecal plasma cells specific for PG and PG-binding antibodies were found in MS CSF during active disease.
Conclusions:
- Peptidoglycan is present in the MS brain and associated with immune-active cells.
- Peptidoglycan may contribute to T-cell and B-cell activity in MS-related brain inflammation.
- This occurs without the need for local bacterial replication in the central nervous system.