Cxcr5-deficient mice are protected during acute infection with C. difficile. (A) Schematic showing timeline of C. difficile infection protocol. Body weight variation (B) and clinical score (C) of WT and Cxcr5−/− mice infected with C. difficile (n = 11). (D and E) Frequencies of cytokine-producing, LTi-like, DN, and NKp46+ ILC3 that were isolated from SIs of C. difficile-infected WT and Cxcr5−/− mice on day 2 of infection and stimulated in vitro with 1 ng/mL IL-23 (n = 4). (F) FITC-dextran in serum of infected mice at day 2 of infection. Mice were bled 4 h after FITC-dextran administration by oral gavage (n = 4). Percentage of initial body weight (G) and clinical scores (H) of infected WT and Cxcr5−/− mice treated with either anti-IL-22–blocking antibody or isotype control (n = 6 to 8). Bar graphs show mean ± SEM. *P < 0.05, **P < 0.01, and ****P < 0.0001 (unpaired Student’s t test). ns, not significant. Data shown are pooled from two independent experiments (B, C, G, and H) or are representative of two (F) or three independent experiments (D–E).