Fig. 4: Enteric neuro/immuno gene expression profiles associated with T. cruzi infection and benznidazole treatment outcomes.

a Volcano plots of the log2-transformed fold change and significance (−log10 P-value) of differentially expressed genes (DEGs) in colon tissue from infected (red/orange shades), benznidazole (BZ) treated and cured (BZ-Cured; blue shades) and BZ-treated and relapsed (BZ-Relapsed; purple shades) vs. uninfected control C3H/HeN mice; and BZ-Cured vs. infected (green shades) mice. Darker coloured shaded dots indicate statistical significance of P < 0.05 (above dashed horizontal line) and lighter shaded dots P < 0.001 (above dotted horizontal line). b Venn diagrams show same-direction differentially expressing genes (DEG) shared between infected, BZ-Cured and BZ-Relapsed for all genes analysed (left, n shows number of genes) and transcription factors (right) (threshold of P < 0.05 vs uninfected controls in at least one group). Arrows indicate up- and down-regulation. c, Relative change in neuro-glial genes between indicated experimental groups; colour intensity indicates fold change (log2) expression vs uninfected controls. d Signalling pathway scores for each group. e Comparison of directionality and extent of gene expression change in chronically infected and BZ-Cured mice vs. uninfected controls (n = 163 genes that are significant DEGs in at least one group). Red circles are DEGs specific to chronic, untreated infections, blue triangles are DEGs specific to the BZ-Cured mice and grey squares are DEGs shared by both groups. Diagonal dashed line is the line of equivalence. Vertical and horizontal dashed lines indicate the position of genes with identical expression levels as uninfected controls in chronic infection and BZ-Cured mice respectively. Infected and uninfected controls n = 6, BZ-Cured and BZ-Relapsed n = 3. Statistical significance was determined by a 2-tailed, unpaired Student’s t-test for each gene. Only significant differences are annotated: *P < 0.05, **P < 0.01, ***P < 0.001, **** P < 0.0001.