Figure 1: Natural variation of macrophage activation in response to LPS in humans and inbred mouse strains.
(a) Human alveolar macrophages were RNA sequenced after intrabronchial instillation of LPS or saline in seven healthy individuals. The fold change gene expression between LPS and control of key genes (columns) of the Toll-like receptor- (total 69 genes) and NF-κB signalling (total 155 genes) pathways are plotted for each volunteer (rows) using Ingenuity. Data derived from GSE40885. (b) Activity score (z score) was calculated by Ingenuity based on matched and predicted induction of downstream gene expression after LPS treatment in the NF-κB and TLR pathway. Data sorted ascendingly by NF-κB activity score. (c,d) Thioglycollate-elicited peritoneal macrophages of 11 mouse strains of the hybrid mouse diversity panel were treated with LPS or PBS and their transcriptome was analysed by Affymetrix Array. Pathway analysis similar to a+b. (e) Arginase (Arg-1), iNOS (Nos-2) and IL-12β (p40) gene expression as RMA (robust multi-array average: quantile normalized, background-corrected, log2 transformed intensities) of human alveolar macrophages of 23 healthy human volunteers at baseline. The induction of gene expression (log2 fold change) after LPS treatment is shown in the bar chart. The dashed lines indicate the median. Baseline data from GSE27002, LPS-data from GSE40885. (f) Thioglycollate-elicited peritoneal macrophages (baseline and LPS-treated) of 26 classical recombinant mouse strains were analysed as described in e.
