Document Type
Article
Journal Title
JCI Insight
Publication Date
2025
Volume
10
Abstract
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 either subset in Rag1-/- animals during early infection prevented S. aureus outgrowth. scRNA-Seq identified a robust IFN signature in several innate immune clusters, and examination of cell-to-cell interactions revealed extensive T cell crosstalk with monocytes/macrophages that was also observed in human craniotomy infection. A cooperative role for Th1 and Th17 responses was demonstrated by treatment of Ifng-/- mice with IL-17A neutralizing antibody that recapitulated phenotypes in Rag1-/- animals. Collectively, these findings implicate Th1- and Th17-mediated proinflammatory responses in shaping the innate immune landscape for S. aureus containment during craniotomy infection.
MeSH Headings
Animals, Mice, Staphylococcal Infections, Immunity, Innate, Staphylococcus aureus, Humans, Craniotomy, CD4-Positive T-Lymphocytes, Th17 Cells, Th1 Cells, Mice, Knockout, Disease Models, Animal, Female, Mice, Inbred C57BL, Male, Brain, Homeodomain Proteins
DOI Link
ISSN
2379-3708
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Recommended Citation
Kak, Gunjan; Van Roy, Zachary A.; Fallet, Rachel W.; Korshoj, Lee E.; and Kielian, Tammy, "CD4+ T Cell-Innate Immune Crosstalk is Critical during Staphylococcus aureus Craniotomy Infection" (2025). Journal Articles: Pathology and Microbiology. 115.
https://digitalcommons.unmc.edu/com_pathmicro_articles/115