Fig 1: Abolishing LTβR promotes infectivity and pathogenesis of B. garinii. (A) Expression analysis of LTA and Lta in THP-1 cells and mouse BMDMs, respectively, post B. garinii infection (MOI 1) for 12 h. Data represent mean ± SEM; ***P < 0.001 by unpaired t test. (B) Ltbr−/− and WT control C3H/HeJ mice were challenged with an intradermal inoculation of 2 × 103 B. garinii. B. garinii burden in joints was examined by genomic DNA qRT-PCR analysis at 28 d postinfection. Data represent mean ± SD (n = 8); ***P < 0.001 by unpaired t test. (C) Joint footpad swelling in B. garinii–infected mice at 28 d postinfection. Data represent mean ± SD (n = 5); **P < 0.01 by unpaired t test. (D) Histopathology of joints in mice (n = 5) at 28 d post B. garinii infection. Representative images and arrows show leukocyte infiltration. (Scale bar, 400 μm.) Arthritis index scores are shown (Right). Data represent mean ± SD; *P < 0.05 by unpaired t test. All data represent at least two independent experiments. BG, B. garinii; KO, knockout; NC, negative control.
Fig 2: Paclitaxel response activates canonical interferon response genes.3A) UMAP showing the scRNA-seq landscape for ligand perturbations. IFNB = Interferon-Beta, OSM = Oncostatin-M, NOTCHi_IFNB = Notch inhibitor + Interferon-Beta, NOTCHi = Notch inhibitor, TGFB = Transforming Growth Factor Beta, IFNG = Interferon-Gamma, LTA = Lymphotoxin-Alpha, PBS = Phosphate Buffered Saline (control). 3B) Heatmap showing the Pearson correlation for all gene log2 fold-change between perturbation versus time-matched control. Inset number and color indicate correlation. 3C,D) Gene enrichment map for Paclitaxel uniquely upregulated (3C) and Paclitaxel+Interferon shared upregulated (3D) genes. Color indicates significance, size indicates number of upregulated genes, and lines connect ontologies with shared elements. 3E) ChEA3 transcription factor enrichment ranks computed from 140 Paclitaxel uniquely upregulated genes (x axis) versus 120 Paclitaxel-Interferon shared upregulated genes (y axis). Lower rank indicates higher imputed activity. TFs to the lower right of the diagonal have higher imputed activity within the PTX+IFN shared upregulated gene set, and TFs to the upper left of the diagonal have higher imputed activity within the PTX uniquely upregulated gene set. 3F) Bar plot showing Average Log2FC from paclitaxel treated scRNA-seq data for the 24 top ranked transcription factors (intersect of top 15 ranked for PTX unique or PTX shared individually). Transcription factor names in red had differential upregulation (average log2 fold-change > 0.25, FDR < 0.01) at either 24 or 72 hours of paclitaxel treatment compared to vehicle control.
Fig 3: Paclitaxel response activates canonical interferon response genes. (A) UMAP showing the scRNA-seq landscape after ligand perturbations. IFNB = Interferon-Beta, OSM = Oncostatin-M, NOTCHi_IFNB = Notch inhibitor + Interferon-Beta, NOTCHi = Notch inhibitor, TGFB = Transforming Growth Factor Beta, IFNG = Interferon-Gamma, LTA = Lymphotoxin-Alpha, PBS = Phosphate Buffered Saline (control). (B) Heatmap showing the Pearson correlation for log2 fold-change values for each perturbation versus time-matched control. (C,D) Gene enrichment map for Paclitaxel uniquely upregulated (3C) and Paclitaxel + Interferon shared upregulated (3D) genes. Color indicates significance, size indicates number of upregulated genes, and lines connect ontologies with shared elements. (E) ChEA3 transcription factor enrichment ranks computed from 140 Paclitaxel uniquely upregulated genes (x axis) versus 120 Paclitaxel-Interferon shared upregulated genes (y axis). Lower rank indicates higher imputed activity, and named TFs with red dots were within the top 15 ranks for either geneset. TFs to the lower right of the diagonal have higher imputed activity within the PTX + IFN shared upregulated gene set, and TFs to the upper left of the diagonal have higher imputed activity within the PTX uniquely upregulated gene set. (F) Bar plot showing Average Log2FC from paclitaxel treated scRNA-seq data for the 24 top ranked transcription factors (intersect of top 15 ranked for PTX unique or PTX shared individually). Red font indicates TFs significantly upregulated (average log2 fold-change > 0.25, FDR < 0.01) at either 24 or 72 h of paclitaxel treatment compared to vehicle control.
Supplier Page from R&D Systems, a Bio-Techne Brand for Recombinant Human Lymphotoxin alpha1/beta2 Protein