An essential role for CD4 +T cells during <i>Staphylococcus aureus</i>craniotomy infection

Abstract Treatment of brain tumors, epilepsy, or hemodynamic abnormalities requires a craniotomy to access the brain. Despite prophylaxis, infectious complications after range from 1–3% with approximately half caused by Staphylococcus aureus(S. aureus). Using our novel mouse model infection, critical role CD4 +T cells was established since bacterial burdens were significantly increased in brain, galea, and bone flap RAG1 −/−mice as well following cell depletion. Bacterial also anti-VLA-4 &amp; LFA-1 treatment, further establishing beneficial for peripheral +infiltrates. Adoptive transfer vitroskewed Th1 Th17 into returned back wild type (WT) levels. Ex vivostaining transferred recovered brains revealed dominant IFN-γ signature, even adoptive transfer, suggesting that responses are infection containment. Further evidence involvement demonstrated exacerbated Tbet −/−and RORγt −/−mice, respectively. Interestingly, phenotypes not evident either IL-17A/F −/−KO whereas IL-17 −/−or −/−animals mitigated outgrowth combined action Th1- Th17-derived mediators. scRNA-seq identified an IFN-γ-regulated signature (gbp1/5, isg15, irf1, stat1) select microglial infiltrating granulocytic clusters. This suggests T cell-innate immune crosstalk is necessary containment during infection. R01 AI169788