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Effects of Th17 cytokines on microglial responses and the blood-brain barrier following recurrent intranasal Group A Streptococcus infections

ABSTRACT: Peripheral infections can result in neuropsychiatric changes in many contexts, including after recurrent Group A Streptococcus (GAS) infections in children. To explore the underlying mechanisms, here we used an intranasal inoculation model to analyze more than 100,000 cells from the mouse olfactory bulb (OB) and nasal lymphoid tissue by single-cell RNA sequencing (scRNAseq). Upon repeated GAS inoculations, endothelial cells responded by downregulating blood-brain barrier (BBB)-specific genes, and microglia upregulated interferon-response, chemokine and antigen-presentation genes. To determine whether specific Th17 cytokines play distinct roles in producing this phenotype, we administered a neutralizing antibody against interleukin 17A (IL-17A), which decreased microglial expression of interferon-response and chemokine genes, but unexpectedly exacerbated levels of antigen presentation markers. Another Th17 cytokine, granulocyte-macrophage colony-stimulating factor (GM-CSF) rescued a different subset of microglial transcripts.

ORGANISM(S): Mus musculus

PROVIDER: GSE221724 | GEO | 2023/03/14

REPOSITORIES: GEO

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