Fig. 3

Genes and HERV/MaLR modulation following LPS stimulation. a Schematic representation of the dose-dependent LPS challenges known as the endotoxin tolerance model. Biological triplicates of PBMCs from 5 healthy volunteers were cultured and stimulated. Efficiency of stimulations was validated with TNF-α and IL10 quantitation by ELISA (Additional file 4: Figure S3) prior to HERV-V3 microarray experiments. b Heatmap from hierarchical clustering (correlation distance, complete method) of the 1% most variable probesets (all repertoires included), group samples according to their stimulation condition. Non-stimulated (NS), low-dose LPS primed PBMCs (ET), single high-dose lipopolysaccharide challenge (LPS); high-expression level (yellow), low-expression level (blue). c Differential gene and HERV/MaLR expression analysis. The first row shows volcano plots derived from the differential expression analysis; on the left for LPS vs NS (inflammatory context), and on the right for ET vs LPS conditions (immunocompromised/unresponsiveness context). The x-axis represents the log2 fold change values, and the y-axis the log10 adjusted p-values. Each point represents these values for a probeset. Coloured points show the significantly modulated probesets (adjusted p-value < 0.05, log2FC < − 1 (red) or log2FC > 1 (green)). The tables in the middle row present the number of statistically significantly differentially expressed elements, at locus level (DELs) for HERVs/MaLRs and differentially expressed genes (DEGs). Down-modulated loci are in red, up-modulated loci are in green. For HERV/MaLR elements, the name, number of differentially expressed probesets (between brackets) and chromosomal locations (in italic) are indicated (GRCh38 version of genome). For genes, the current gene symbol and the number of differentially expressed probesets (between brackets) are indicated. The last row represents canonical pathways identified using Ingenuity Pathways Analysis tool (https://analysis.ingenuity.com) and signals derived from HTA probesets contained on the HERV-V3 chip. Canonical pathways predicted to be significantly activated (orange) or inhibited (blue) between LPS vs NS and ET vs LPS conditions are depicted (z-scores ≥2 and z-scores ≤ − 2; p-value cut off of 0.05, Fisher’s exact test)