Fig. 1: Localized innate IFN-γ provides early protection from mouse-adapted C. parvum and pathology.

WT mice were infected with 10⁵ maCp-Nluc oocysts and treated with either α-IFN-γ or isotype control. a At 4 dpi, two adjacent 5 mm biopsies were taken along the length of the small and large intestines (D duodenum, J jejunum, I ileum, Ce cecum, and C colon). One biopsy was evaluated for nanoluciferase (top), the other was incubated at 37 °C for 24 h and IFN-γ was measured from the supernatant. Graph depicts 1 representative mouse from n = 3 for each group. b WT C57BL/6 and Rag2^−/− mice were treated with isotype or α-IFN-γ and nanoluciferase was used to measure fecal oocyst shedding, n = 4 per group. Similar results were observed in two additional experiments. c Representative mucosa and (d–g) cumulative histology scoring from Rag2^−/− mice 5 dpi that shows a marked increase in cryptosporidia organisms (black arrows) infecting the villus enterocytes in treated mice versus controls with a progressive increase in epithelial dysplasia (arrowheads), reduced villus:crypt ratios with increased crypt depth (double-headed arrows) and crypt mitoses (white arrows); scale bars = 20 μm. h Rag2^−/− mice were infected with 10⁵ maCp-Nluc oocysts and treated with α-IFN-γ at 50, 53, and 56 dpi. Oocysts shedding was monitored throughout by nanoluciferase. n = 4, representative from three experimental replicates. Bars denote mean ± SD. ANOVA followed by multiple comparisons were performed on cumulative pathology scores, **p ≤ 0.01; ***p ≤ 0.001.