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| Status |
Public on Nov 25, 2024 |
| Title |
CD4+ T cell-innate immune crosstalk is critical during Staphylococcus aureus biofilm infection [CD3+ scRNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Access to the brain for treating neurological sequalae requires a craniotomy, which can be complicated by infection. T cells preferentially home to the brain, but not other tissue sites, during Staphylococcus aureus (S. aureus) craniotomy infection; however, their functional importance is unknown. CD4+ T cells were critical for bacterial containment during craniotomy infection as Rag1-/- mice and WT animals treated with anti-CD4 or VLA-4 and LFA-1 antibodies exhibited elevated bacterial burdens. scRNA-seq revealed transcriptional heterogeneity in brain CD3+ infiltrates, with CD4+ cells most prominent and typified by both Th1 and Th17 signatures, and adoptive transfer of either subset in Rag1-/- mice prevented S. aureus outgrowth. scRNA-seq revealed a profound IFN-γ signature in innate immune cells from Rag1-/- mice during craniotomy infection, supporting extensive T cell-innate immune crosstalk that was validated by immunostaining in the brain parenchyma. A cooperative role for Th1 and Th17 driven responses was demonstrated by treatment of Ifng-/- mice with IL-17A/F neutralizing Ab that recapitulated phenotypes observed in Rag1-/- animals, which were not observed following the loss of either cytokine alone. Collectively, these results implicate a critical role for CD4+ T cells in S. aureus containment during craniotomy infection by shaping the innate immune landscape.
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| Overall design |
To better understand the function of t cells during craniotomy infection, we collected immune cells from a mouse model of craniotomy infection to perform scRNA-seq. CD3+ cells were sorted from brain homogenates of wild-type (C57BL/6) mice subjected to craniotomy infection at days 3,7 and 14 post-craniotomy infections.
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| Contributor(s) |
Kak G, van Roy Z, Fallet R, Korshoj L, Kielian T |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Apr 23, 2024 |
| Last update date |
Nov 25, 2024 |
| Contact name |
Tammy Kielian |
| E-mail(s) |
[email protected]
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| Phone |
14028893038
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| Organization name |
UNMC
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| Street address |
985900 Nebraska Medical Center
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| City |
White/Caucasian |
| State/province |
NE |
| ZIP/Postal code |
68105 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (3) |
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| This SubSeries is part of SuperSeries: |
| GSE264738 |
CD4+ T cell-innate immune crosstalk is critical during Staphylococcus aureus biofilm infection. |
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| Relations |
| BioProject |
PRJNA1103931 |
