Extended Data Fig. 7: IL-4R blockage reduces Giardia-mediated protection against bystander intestinal inflammation.
(a) Experimental schematic. Female WT mice (C57BL/6 background) were perorally infected with 1Ă—106 Giardia GS/M strain trophozoites and three days later mice were perorally co-infected with 10 cysts of Toxoplasma gondii, followed by intraperitoneal injection of anti-IL-4R (50 μg) or anti-IL10R (100 μg) for five consecutive days. Euthanasia was performed 8 days post-Toxoplasma infection (8 d.p.T.i.). Created with BioRender. (b) Body weight loss of WT mice co-infected with Giardia and Toxoplasma followed treatment with isotype control (n = 5), anti-IL-4R (n = 5) or anti-IL-10R (n = 5) were monitored daily. (c) Representative image of H&E staining of the jejunum from WT mice co-infected with Giardia and Toxoplasma treated with isotype control (n = 5), anti-IL-4R (n = 5) or anti-IL-10R (n = 5) and scatter plot graph showing the histopathology score (8 d.p.T.i.). Scale bars represent 500 μm (top) and 300 μm (bottom). (d) Experimental schematic. Female WT mice (C57BL/6 background) were perorally infected with 1Ă—106 Giardia GS/M strain trophozoites and three days later mice were administered 2% DSS drinking water for 7 consecutive days, followed by intraperitoneal injection of anti-IL-4R (50 μg) or anti-IL10R (100 μg) for five consecutive days. Euthanasia was performed on day 8 (8 d.p.t.). Created with BioRender. (e) Body weight loss of WT Giardia-infected and DSS-treated mice followed isotype control (n = 4), anti-IL-4R (n = 5) or anti-IL-10R (n = 5) injection. (f) Representative image of H&E staining of the colon from WT mice Giardia-infected and DSS-treated mice followed isotype control (n = 4), anti-IL-4R (n = 5) or anti-IL-10R (n = 5) injection and scatter plot graph showing the histopathology score (8 d.p.t.). Scale bars represent 500 μm (top) and 300 μm (bottom). Figure symbols in c and f: [*] inflammatory infiltrate in the mucosa; [$] inflammatory infiltrate in the submucosa; [#] inflammatory infiltrate in the muscle layer; [arrow] mucosal ulceration; [short arrow] mucosal desquamation. Data are represented as mean ± SEM and significance was calculated with one-way ANOVA test followed by Sidak’s multiple comparisons test (c,f). *p≤0.05, **p≤0.01, ***p≤0.001, ****p≤0.0001. Data are representative of one independent experiment (n = 5).
