Figure 2.

Infection triggers a hardwired innate immune response. (A) RNAseq was used to identify differentially expressed genes in whole blood at diagnosis (versus baseline) (adj P < 0.05 and >1.5 fold-change). ClueGO was then used for functional gene enrichment analysis and placed significant GO terms into functional groups by relatedness. Shown are the leading GO terms from 15 non-redundant groups with the lowest adj P value in the first infection. The same GO terms are plotted in the second and third infections (note that each infection was analyzed independently). (B) Radar plots (or three-way volcano plots) show the number of differentially expressed genes in whole blood between each infection—the left plot compares all baseline samples and the right plot diagnosis. Dashed lines represent the center point for each volcano plot, and the position of each dot relative to this line shows up- or downregulation. There were no differentially expressed genes in any of the six pairwise comparisons (adj P < 0.05 and >1.5 fold-change [FC]). (C) 39 plasma analytes were quantified before and during each infection using a highly multiplexed bead-based assay. The log₂ fold-change of each analyte is shown relative to baseline on day 6 and 8 after challenge (c6 and c8, respectively) and at diagnosis. Analytes are ordered by log₂ fold-change and are marked with an asterisk if they varied significantly during both the second and third (compared to first) infections (adj P < 0.05 by linear regression with Benjamini–Hochberg correction for multiple testing). In A and B, n = 10 (first infection), 9 (second infection), and 6 (third infection). v1040 was excluded from RNAseq analysis in the second infection because their baseline sample failed QC. In C, n = 9 (first and second infection) and 5 (third infection). v1040 was excluded from plasma analysis because all samples failed QC.