| Autor: |
Charlotte R. Wayne, Luca Bremner, Travis E. Faust, Violeta Durán-Laforet, Nicole Ampatey, Sarah J. Ho, Philip A. Feinberg, Panos Arvanitis, Bogoljub Ciric, Chunsheng Ruan, Wassim Elyaman, Shannon L. Delaney, Wendy S. Vargas, Susan Swedo, Vilas Menon, Dorothy P. Schafer, Tyler Cutforth, Dritan Agalliu |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
|
| Zdroj: |
bioRxiv |
| Popis: |
SUMMARYGroup AStreptococcus(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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
