Fig. 3.

IL-12 is indispensable for low-dose infection of TRPM2^−/− mice. (A) TRPM2^−/− mice can survive a lower dose Lm infection. Kaplan–Meier survival plot of 10 BL6 (squares), 10 TRPM2^−/− (circles), or 6 IFNγR^−/− mice (triangles) infected i.v. with 2 × 10³ Lm. Median survival of IFNγR^−/− mice (4.75 d) was significantly reduced by log rank test (P < 0.0001) compared with BL6 and TRPM2^−/− mice. Data representative of four separate experiments. (B) TRPM2^−/− mice are susceptible to a low-dose Lm infection where IL-12Rβ2^−/− mice are resistant. Kaplan–Meier survival plot of eight BL6 (squares), four TRPM2^−/− (open circles), or four IL-12Rβ2^−/− mice (open triangles), or five IFNγR^−/− mice (closed triangles) infected with 3 × 10³ Lm. Median survival of TRPM2^−/− mice closely matched IFNγR^−/− mice (3.5 d) and both are significant by log rank test (P < 0.0001) compared with BL6 and IL-12Rβ2^−/− mice. Data are representative of two separate experiments. (C) IL-12p40 is indispensable in TRPM2^−/− mice infected with very low doses of Lm. Kaplan–Meier survival plot of BL6 (squares), TRPM2^−/− (circles), or IFNγR^−/− mice (triangles) infected i.v. with 1 × 10³ Lm (five to eight mice each group). Three hours before infection, BL6 or TRPM2^−/− mice were i.p. injected with 1.5 mg neutralizing mAb against IL-12p40 (white) or rat isotype control IgG_2A (black). Median survival of IFNγR^−/− mice (7.75 d) was significant by log rank test (P < 0.005) compared with BL6 and TRPM2^−/−. Data are representative of two separate experiments.