Biphasic effects of pleiotropic cytokine IL-27 during Staphylococcus aureus implant-associated osteomyelitis
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE168896 | GEO | 2021/03/16
REPOSITORIES: GEO
Similar Datasets
Project description:Biphasic effects of pleiotropic cytokine IL-27 during Staphylococcus aureus implant-associated osteomyelitis
| PRJNA714525 | ENA
Project description:Objective: To investigate the molecular pathogenesis of bone with implant-associated osteomyelitis (IAOM) in early and chonic stages. Methods: After a 2 mm sterile stainless pin (0.3 mm in diameter) was inserted into the bone marrow cavity, 2 μl S. aureus solution at 1 × 10e6 CFU/ml was slowly injected into the bone marrow cavity using a micro-syringe to create IAOM mice while only an equal volume of sterile PBS to create controls. Transcriptomic sequencing was performed on day 3 and 14 post-operation, respectively. Differential expression analyses of IAOM_3D vs Ctrl_3D and of IAOM _14D vs Ctrl_14D were performed using the DESeq2 R package (1.16.1); P-values were adjusted using the Benjamini and Hochberg’s approach to control the false discovery rate. The genes with an adjusted P-value < 0.05 and |log2 (Fold Change)| > 1 were recognized as differentially expressed genes (DEGs). GO, KEGG and PPI analysis of DEGs were performed to identify key genes. Results: Differential expression analyses detected a total of 101 DEGs, among which 96 were up-regulated and 5 down-regulated in the femur, when the IAOM and control groups were compared by day 3 post-infection. The number of DEGs significantly increased up to 1,702 by day 14 post-operation, with 1,065 up-regulated and 637 down-regulated in the IAOM femurs compared with controls. Further GO, KEGG and PPI analyses of DEGs suggested that IL-6, CXCL10, IFN-γ and CXCL9 were associated with early development of IAOM. Conclusions: Our study has revealed transcriptomic characteristics of IAOM and suggested that IL-6, CXCL10, IFN-γ and CXCL9 might play an important role in the early stage of IAOM.
2021-02-11 | GSE166522 | GEO
Project description:To explore how APOE functions in the mechanism of regulation of cholesterol metabolism during S. aureus osteomyelitis, we established S. aureus osteomyelitis models in WT mice and APOE knockout mice. We then performed gene expression profiling analysis using data obtained from RNA-seq of bone marrow from mice mentioned above at day 7 after operation.
2023-07-09 | GSE227521 | GEO
Project description:Staphylococcus aureus is Gram-positive commensal bacteria that can also cause human disease ranging from mild, self-resolving skin infections to life-threatening conditions like endocarditis, osteomyelitis, and septicemia. Previously we demonstrated a role for the S. aureus sRNA, Teg41 in regulating production of the alpha Phenol Soluble Modulin toxins (αPSMs). In this study, we further characterize the regulatory role of Teg41. RNAseq analysis shows Teg41 influences the abundance of not just the αPSM transcript, but a variety of other transcripts as well compared to wild type S. aureus. Proteomic analysis confirms that eliminating Teg41 from the cell influences both the cytoplasmic and secreted protein profile of S. aureus. Finally, we observe that the Teg41Δ3′ strain is more severely attenuated in two murine infection models than a ∆αPSM strain, indicating that Teg41 regulation reaches beyond the αPSMs. Overall, we show that Teg41 is a unique pleiotropic sRNA in S. aureus that influences several key cellular processes.
2022-09-29 | GSE203564 | GEO
Project description:Staphylococcus aureus is Gram-positive commensal bacteria that can also cause human disease ranging from mild, self-resolving skin infections to life-threatening conditions like endocarditis, osteomyelitis, and septicemia. Previously we demonstrated a role for the S. aureus sRNA, Teg41 in regulating production of the alpha Phenol Soluble Modulin toxins (αPSMs). In this study, we further characterize the regulatory role of Teg41. RNAseq analysis shows Teg41 influences the abundance of not just the αPSM transcript, but a variety of other transcripts as well compared to wild type S. aureus. Proteomic analysis confirms that eliminating Teg41 from the cell influences both the cytoplasmic and secreted protein profile of S. aureus. Finally, we observe that the Teg41Δ3′ strain is more severely attenuated in two murine infection models than a ∆αPSM strain, indicating that Teg41 regulation reaches beyond the αPSMs. Overall, we show that Teg41 is a unique pleiotropic sRNA in S. aureus that influences several key cellular processes.
2022-09-29 | GSE203563 | GEO
Project description:Staphylococcus aureus is Gram-positive commensal bacteria that can also cause human disease ranging from mild, self-resolving skin infections to life-threatening conditions like endocarditis, osteomyelitis, and septicemia. Previously we demonstrated a role for the S. aureus sRNA, Teg41 in regulating production of the alpha Phenol Soluble Modulin toxins (αPSMs). In this study, we further characterize the regulatory role of Teg41. RNAseq analysis shows Teg41 influences the abundance of not just the αPSM transcript, but a variety of other transcripts as well compared to wild type S. aureus. Proteomic analysis confirms that eliminating Teg41 from the cell influences both the cytoplasmic and secreted protein profile of S. aureus. Finally, we observe that the Teg41Δ3′ strain is more severely attenuated in two murine infection models than a ∆αPSM strain, indicating that Teg41 regulation reaches beyond the αPSMs. Overall, we show that Teg41 is a unique pleiotropic sRNA in S. aureus that influences several key cellular processes.
2022-10-03 | PXD034014 | Pride
Project description:IL-6 and IL-27 have antagonistic and overlapping functions, signal through a shared receptor subunit and employ the same downstream STAT proteins. To evaluate the degree of specificity and redundancy for these cytokines, we quantified global transcriptomic changes induced by the two cytokines and determined the relative contributions of STAT1 and STAT3 using genetic models and ChIP-seq. We found a high degree of overlap of the transcriptomes induced by IL-6 and IL-27 and extremely few examples in which the cytokines acted in opposition. Using STAT deficient cells and T cells from patients with gain-of-function STAT1 mutations, we show that STAT3 was responsible for the overall transcriptional output driven by both cytokines, whereas STAT1 was the driver of cytokine specificity. STAT1 did not compensate for the lack STAT3; on the contrary, much of STAT1 binding to chromatin was STAT3 dependent. Thus, STAT1 shapes the specific cytokine signature superimposed upon STAT3’s action. Integrated analysis of transcriptome and transcription factor binding data from cytokine treated CD4+T cells
2015-05-27 | E-GEOD-65621 | biostudies-arrayexpress
Project description:IL-6 and IL-27 have antagonistic and overlapping functions, signal through a shared receptor subunit and employ the same downstream STAT proteins. To evaluate the degree of specificity and redundancy for these cytokines, we quantified global transcriptomic changes induced by the two cytokines and determined the relative contributions of STAT1 and STAT3 using genetic models and ChIP-seq. We found a high degree of overlap of the transcriptomes induced by IL-6 and IL-27 and extremely few examples in which the cytokines acted in opposition. Using STAT deficient cells and T cells from patients with gain-of-function STAT1 mutations, we show that STAT3 was responsible for the overall transcriptional output driven by both cytokines, whereas STAT1 was the driver of cytokine specificity. STAT1 did not compensate for the lack STAT3; on the contrary, much of STAT1 binding to chromatin was STAT3 dependent. Thus, STAT1 shapes the specific cytokine signature superimposed upon STAT3’s action.
2015-05-27 | GSE65621 | GEO
Project description:The pleiotropic cytokine IL-27 is essential for the clearance of the persistent LCMV strain Clone 13, however the cellular sources of IL-27 during viral infection are incompletely mapped and their relative importance unknown. Here we utilised single-cell RNA-sequencing of splenocytes from IL27-p28-GFP mice infected with Clone 13 to quantify the temporal patterns of IL-27 p28 production. IL-27-p28-GFP+ and IL-27-p28-GFP- splenocytes were sorted at 4 timepoints during Clone 13 infection and analysed by 3' single-cell transcriptome sequencing. Dendritic cells were major producers of early IL-27 with macrophages and monocytes being the predominant IL-27 producers during acute and persistent phases of infection. Interestingly, we also identified activated B cells and plasma cells as a prominent subset of IL-27-producing splenocytes and through B-cell-specific deletion of IL-27-p28 demonstrated that B-cell derived IL-27 is essential for sustained function of CD4 T cells and eventual clearance of Clone 13.
2022-01-10 | GSE186898 | GEO
Project description:Staphylococcus aureus subsp. aureus AA-27 Genome sequencing
| PRJNA53843 | ENA