Figure 1.
Blood transcriptional responses following in vitro exposure to purified TLR or IL-1R agonists. (a) Changes in expression levels of transcripts responsive to TIR agonists are represented on a heatmap. Blood from healthy controls or patients was stimulated in vitro for 2 hours with TLR agonists and cytokines (batch 1); responsive transcripts were arranged by rows via hierarchical clustering (1784, 500 and 237 for PMA + ionomycin, LPS and PAM2 stimulations, respectively), and individual subjects by columns from left to right: healthy controls (n=14), MYD88−/− patients (n=4), IRAK4−/− patients (n=4). Changes versus the non-stimulated condition are represented by a color scale: red = up-regulated; blue = down-regulated; yellow = no change. Bar graphs represent overall individual levels of responsiveness relative to the average of controls: the number of responsive probes in a given subject/average of differentially expressed probes in healthy controls x100. Responses to 8 additional TIR agonists and TNF are presented similarly in Supplementary Fig 2a. (b). The overall responsiveness of individual subjects along the horizontal axis relative to the average of controls is shown across all TIR ligand stimulations on a heatmap. Subjects and stimulations were grouped by hierarchical clustering.