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Modeling Multiple Sclerosis in the Two Sexes: MOG35-55-Induced Experimental Autoimmune Encephalomyelitis
Published on: October 13, 2023
Streptococcus pneumoniae Infection aggravates experimental autoimmune encephalomyelitis via Toll-like receptor 2
Isabel Herrmann1, Markus Kellert, Hauke Schmidt
1Department of Neurology, Georg August University, Robert-Koch-Str. 40, D-37075 Göttingen, Germany.
Abstract:
The course of autoimmune inflammatory diseases of the central nervous system (CNS) can be influenced by infections. Here we assessed the disease-modulating effects of the most frequent respiratory pathogen Streptococcus pneumonia on the course of experimental autoimmune encephalomyelitis (EAE). Mice were immunized with myelin oligodendrocyte glycoprotein 35-55 (MOG(35-55)) peptide, challenged intraperitoneally with live S. pneumoniae type 3, and then treated with ceftriaxone. EAE was monitored by a clinical score for 35 days after immunization. EAE was unaltered in mice infected with S. pneumoniae 2 days before and 21 days after the first MOG(35-55) injection but was more severe in animals infected 7 days after the first MOG(35-55) injection. The antigen-driven systemic T-cell response was unaltered, and the intraspinal Th1 cytokine mRNA concentrations at the peak of disease were unchanged. The composition of CNS-infiltrating cells and subsequent tissue destruction were only slightly increased after S. pneumoniae infection. In contrast, the serum levels of tumor necrosis factor alpha and interleukin-6 and spinal interleukin-6 levels were elevated, and the expression of major histocompatibility complex class II molecules, CD80, and CD86 on splenic dendritic cells were enhanced early after infection. Serum cytokine concentrations were not elevated, and EAE was not aggravated by S. pneumoniae infection in Toll-like receptor 2 (TLR2)-deficient mice. In conclusion, infection with S. pneumoniae worsens EAE probably by elevation of proinflammatory cytokines and activation of dendritic cells in the systemic circulation via TLR2 and cross talk through the blood-brain barrier.
Insights
Infections with Streptococcus pneumoniae can worsen experimental autoimmune encephalomyelitis (EAE) by increasing inflammation and activating immune cells, particularly via Toll-like receptor 2 (TLR2). This highlights a potential link between common infections and central nervous system (CNS) autoimmune diseases.
Area of Science:
- Neuroimmunology
- Infectious Disease Immunology
- Autoimmune Disorders
Background:
- Infections can influence the progression of central nervous system (CNS) autoimmune diseases.
- Streptococcus pneumoniae is a common respiratory pathogen with potential immunomodulatory effects.
Purpose of the Study:
- To investigate the impact of Streptococcus pneumoniae infection on experimental autoimmune encephalomyelitis (EAE), a model for CNS autoimmune inflammation.
- To elucidate the mechanisms by which S. pneumoniae affects EAE severity and associated immune responses.
Main Methods:
- Mice were immunized with myelin oligodendrocyte glycoprotein (MOG(35-55)) peptide to induce EAE.
- Mice were infected with live S. pneumoniae type 3 at different time points relative to immunization.
- EAE clinical scores, cytokine levels, CNS-infiltrating cells, and dendritic cell activation markers were analyzed.
- Experiments were also conducted in Toll-like receptor 2 (TLR2)-deficient mice.
Main Results:
- S. pneumoniae infection exacerbated EAE when administered 7 days after MOG(35-55) immunization.
- Infection led to elevated serum and spinal pro-inflammatory cytokines (TNF-α, IL-6) and enhanced dendritic cell activation (MHC class II, CD80, CD86).
- EAE exacerbation and associated immune changes were dependent on Toll-like receptor 2 (TLR2) signaling.
Conclusions:
- Streptococcus pneumoniae infection can worsen EAE, likely through TLR2-mediated activation of dendritic cells and subsequent elevation of pro-inflammatory cytokines.
- These systemic changes may cross-talk with the CNS via the blood-brain barrier, contributing to increased disease severity.
- The findings suggest a role for common bacterial infections in modulating CNS autoimmune disease activity.
