Xiap−/− mice exhibit heightened sensitivity to C albicans infection. (A-B) Poor survival of Xiap−/− mice following C albicans infection. C albicans (1 × 106) was intravenously administered to (A) 8- to 10-week-old and (B) 16-week-old WT and Xiap−/− mice. Survival of mice is presented by a Kaplan-Meier survival curve; n = 7 for A and B. (C) Reduced inflammatory cytokine production in Xiap−/− mice after C albicans infection. Serum from mice in A and B was collected 4 hours after C albicans injection, and the levels of IL-6, MCP-1, and TNF-α were determined; n = 10, 3 mice from A and 7 mice from B. (D) Poor survival of Xiap−/− mice following a low dose of C albicans infection. WT and Xiap−/− mice (8-12 weeks old) were intravenously injected with C albicans (1 × 105), and the survival of mice was monitored; n = 6. (E) Morphology of kidney from WT and Xiap−/− mice infected with low doses of C albicans. WT and Xiap−/− mice were intravenously injected with C albicans (1 × 105). Infected Xiap−/− mice were euthanized on 30% loss of body weight. Kidneys were isolated from Xiap−/− mice and WT mice infected at the same time (days 8-12 after infection). Two pairs of kidney (of 5) are shown. (F) Elevated neutrophil infiltration in C albicans-infected Xiap−/− mice kidney. Total kidney cells were prepared from the kidneys in E and stained with anti-F4/80 and anti-Gr-1, and the fraction of the macrophages (Gr-1−/intF4/80+) and neutrophils (Gr-1+F4/80−) was analyzed by flow cytometry. (G) Highly increased fungal burden in Xiap−/− mice infected with C albicans. Livers, kidneys, and spleens were removed from C albicans-infected WT and Xiap−/− mice in D between days 8 and 12. Colony-forming units of C albicans in each organ was determined. (H) Elevated inflammatory cytokine in Xiap−/− mice 1 week after C albicans infection. Serum from mice in D was collected 7 days after C albicans (1 × 105) injection, and the levels of IL-6, TNF-α, and MCP-1 were determined. *P < .05, **P < .01, and ***P < .001 for paired Student t test.
