CD14 and Complement Crosstalk and Largely Mediate the Transcriptional Response to Escherichia coli in Human Whole Blood as Revealed by DNA Microarray
Fig 3
Crosstalk between CD14- and C3-dependent responses.
Crosstalk between CD14 and C3 was assumed when the sum of single inhibitory effects was significantly different from the inhibitory effect of combined inhibition in ANOVA-based interaction effect analyses. This scenario was found for 251 ERGs, designated IAEs. A, The Venn diagram shows the distribution of ERGs with significant effects (ANOVA-based analysis) of single CD14 or C3 inhibition among the 251 IAE genes. Common genes are encompassed by more than one circle. The total numbers for IAEs with significant effects of C3- or CD14-inhibition were 223 and 125, respectively. IAE genes with both single and combined inhibitory effects (n = 110) were designated IAE-I. Numbers of IAEs without single inhibitory effects are indicated at the bottom right of the diagram (n = 13). B, The graph displays the distribution of IAE-I genes among six classes of crosstalk between CD14 and C3 including synergy, four types of counteraction and redundancy. The different crosstalk types were defined according to individual profiles of reversion and augmentation of the E. coli response upon single and combined inhibition using Limma-derived expression data. C, Hierarchical cluster analysis was based on Limma-derived log2FC expression values for the E. coli response of the 251 IAE genes in the absence (E. coli) and presence of the inhibitors of C3, CD14 or both. Each line contains the fold change (FC) expression data (log2FC) for a single ERG. Genes with similar responses are clustered according to the hierarchy indicated to the left. Manual examination of the heat map revealed six main clusters of related either down- (clusters 1 and 2) or up-regulated ERGs (clusters 3 to 6). The color key and histogram panel indicate total numbers of transcripts contained by the whole gene expression dataset as a function of their log2FC expression values. Negative values are displayed in blue, positive values are displayed in red.