biostudies-literatureKak GNational Institute of Allergy and Infectious DiseasesNational Institute of Neurological Disorders and StrokeNIAID NIH HHSNCI NIH HHSNINDS NIH HHSNIGMS NIH HHSe183327https://www.ebi.ac.uk/biostudies/studies/S-EPMC11949042biostudies-literatureUnknown10(4)Access to the brain for treating neurological sequalae requires a craniotomy, which can be complicated by infection. Staphylococcus aureus accounts for half of craniotomy infections, increasing morbidity in a medically fragile patient population. T cells preferentially traffic to the brain during craniotomy infection; however, their functional importance is unknown. Using a mouse model of S. aureus craniotomy infection, CD4+ T cells were critical for bacterial containment, as treatment of WT animals with anti-CD4 exacerbated infection that was similar to phenotypes in Rag1-/- mice. Single-cell RNA-Seq (scRNA-Seq) revealed transcriptional heterogeneity in brain CD3+ infiltrates, with CD4+ cells most prominent that displayed Th1- and Th17-like characteristics, and adoptive transfer of eitherJCI insightCD4+ T cell-innate immune crosstalk is critical during Staphylococcus aureus craniotomy infection.PMC11949042P30 CA036727R01 AI169788F32 NS126302P30 GM110768P20 GM103427Kak GFallet RWVan Roy ZKielian TKorshoj LEfalseCD4+ T cell-innate immune crosstalk is critical during Staphylococcus aureus craniotomy infection.Access to the brain for treating neurological sequalae requires a craniotomy, which can be complicated by infection. Staphylococcus aureus accounts for half of craniotomy infections, increasing morbidity in a medically fragile patient population. T cells preferentially traffic to the brain during craniotomy infection; however, their functional importance is unknown. Using a mouse model of S. aureus craniotomy infection, CD4+ T cells were critical for bacterial containment, as treatment of WT animals with anti-CD4 exacerbated infection that was similar to phenotypes in Rag1-/- mice. Single-cell RNA-Seq (scRNA-Seq) revealed transcriptional heterogeneity in brain CD3+ infiltrates, with CD4+ cells most prominent that displayed Th1- and Th17-like characteristics, and adoptive transfer of either2025-01-01T00:00:00Z2025 Feb2026-06-02T17:29:48.449Z2025-06-25T03:04:38.457ZS-EPMC119490423998946110.1172/jci.insight.183327