Fig. 6: Collagen experienced HIV-1 virions are sensitized for TLR2 and TLR8 recognition in MDMs, reshaping their transcriptional landscape.

a Schematic representation of PRRs and their cognate ligands. PRRs: green, adapter proteins: pink, PAMPs: red, transcription factors: blue. b PRR inhibitor screening. MDMs were challenged with S or DC HIV-1 NL4.3 R5 virions in presence or absence of PRR inhibitors. IL-6 release was measured by ELISA from MDM supernatants. Data is normalized to mock infected condition (gray dotted line). c Measurement of IL-6 release from the supernatants of MDMs challenged with S or DC HIV-1 virions in presence or absence of the indicated inhibitors. d Volcano plot illustrating the differential gene expression between MDMs challenged with DC virus and mock challenged cells for 6 h. The number of down- and upregulated genes are indicated. e Volcano plot as in d. with highlighted gene signatures. Genes induced by TLR2 alone (blue), TLR8 alone (brown), co-regulated (light green) or associated with “Innate Immune Response” genes (red). f Volcano plot illustrating the differential gene expression between MDMs challenged with suspension or collagen primed HIV-1 virus for 6 h. The number of down- and upregulated genes are indicated. g Volcano plot as in f. with highlighted gene signatures. Genes induced by TLR2 alone (blue), TLR8 alone (brown), co-regulated (light green) or associated with Innate Immune Response genes (red). Top deregulated genes belonging to different gene ontology terms are highlighted. h Gene ontology analysis of biological processes repressed or induced in MDMs challenged with collagen primed virions as compared to cells challenged with suspension virus for 6 h. FDR is indicated (only upregulated pathways have a q-value < 0.05). Top deregulated genes for each pathway are highlighted. Results represent the mean ± SD of 3 independent donors. Symbols indicate individual donors (b, c) or individual genes (d–g). Significance is indicated by p-values, and was calculated by two-tailed paired t-tests or Wilcoxon matched-pairs signed rank test (b, c), differential gene expression analysis was performed using DESeq2: genes with adjusted p-value < 0.05 were considered significant (d–g), for GSEA analysis, p-values were corrected using Benjamini-Hochberg FDR (h). Source data are provided as a Source Data file.