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Updated: Jul 29, 2025
Visualizing Impairment of the Endothelial and Glial Barriers of the Neurovascular Unit during Experimental Autoimmune Encephalomyelitis In Vivo
Published on: March 26, 2019
Distinct Th17 effector cytokines differentially promote microglial and blood-brain barrier inflammatory responses
Insights
Group A Streptococcus infections can lead to neuropsychiatric issues in children. Interleukin-17A (IL-17A) drives these effects by impacting brain cells and the blood-brain barrier (BBB), offering a potential therapeutic target.
Area of Science:
- Neuroscience
- Immunology
- Microbiology
Background:
- Group A Streptococcus (GAS) infections in children can cause post-infectious encephalitis, leading to neuropsychiatric sequelae.
- Th17 lymphocytes migrating to the brain are implicated in microglial activation and blood-brain barrier (BBB) impairment following GAS infections.
Approach:
- Utilized single-cell RNA sequencing and spatial transcriptomics to investigate endothelial cell (EC) and microglia responses to GAS.
- Analyzed Th17-derived cytokines critical for these cellular responses in a mouse model.
Key Points:
- GAS infection alters ECs by downregulating BBB genes and microglia by upregulating interferon-response, chemokine, and antigen-presentation genes.
- Elevated microglial-derived chemokines were detected in patient sera.
- Neutralizing interleukin-17A (IL-17A) partially restored BBB function and reduced microglial chemokine gene expression.
Conclusions:
- Interleukin-17A (IL-17A) plays a critical role in the neuropsychiatric sequelae associated with GAS infections.
- Targeting IL-17A presents a potential therapeutic strategy for treating these post-infectious neurological disorders.
Abstract:
Group A Streptococcus (GAS) infections can cause neuropsychiatric sequelae in children due to post-infectious encephalitis. Multiple GAS infections induce migration of Th17 lymphocytes from the nose into the brain, which are critical for microglial activation, blood-brain barrier (BBB) and neural circuit impairment in a mouse disease model. How endothelial cells (ECs) and microglia respond to GAS infections, and which Th17-derived cytokines are essential for these responses are unknown. Using single-cell RNA sequencing and spatial transcriptomics, we found that ECs downregulate BBB genes and microglia upregulate interferon-response, chemokine and antigen-presentation genes after GAS infections. Several microglial-derived chemokines were elevated in patient sera. Administration of a neutralizing antibody against interleukin-17A (IL-17A), but not ablation of granulocyte-macrophage colony-stimulating factor (GM-CSF) in T cells, partially rescued BBB dysfunction and microglial expression of chemokine genes. Thus, IL-17A is critical for neuropsychiatric sequelae of GAS infections and may be targeted to treat these disorders.
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