Fig. 4. Chemical cartography reveals a causal role for carnitine metabolism in acute CD tolerance.

(A) Acylcarnitine molecular network (all tissue sites and time points combined). (B) Infection-induced increases in acute-stage long-chain acylcarnitines in the distal small intestine (black lines, FDR-corrected Mann-Whitney P < 0.05). (C) Spatial distribution of acute-stage long-chain acylcarnitines [medians; common logarithmic scale from lowest (dark blue) to highest abundance (dark red)]. *Above sampling sites, P < 0.05 FDR-corrected Mann-Whitney. (D) Carnitine treatment prevents acute-stage mortality (n = 5 per group, 50,000 trypomastigote infection). (E and F) Comparable parasite burden between carnitine-treated and vehicle groups. (E) Overall whole-body luminescence. Mean and SEM are displayed. (F) Representative bioluminescent imaging, week 3 after infection (common scale). (G and H) Carnitine treatment mitigates plasma infection-induced metabolic disturbances (n = 24 benznidazole and carnitine groups, n = 22 vehicle group, and n = 9 uninfected group). (G) PCoA analysis (Bray-Curtis-Faith distance metric) of plasma samples. (H) Heat map showing metabolite features distinguishing vehicle-treated individuals from carnitine-treated, benznidazole-treated, and uninfected individuals (Kruskal-Wallis, FDR-corrected P < 0.05). (I) Carnitine treatment mitigates cardiac infection-induced metabolic disturbances. PCoA analysis (Bray-Curtis-Faith distance metric) of heart samples [n = 5 for uninfected, vehicle, and carnitine groups; n = 4 for benznidazole group (one biological replicate; see fig. S6D for data from second replicate)]. (J) Carnitine treatment reduces cardiac Bnp gene expression (n = 10 for benznidazole group and carnitine group, n = 9 for vehicle group, and n = 4 for uninfected group; Student’s t test P = 0.01).