Fig 7.
Abl family kinases permit efficient infection in a mouse model of cutaneous leishmaniasis. (A) Imatinib-treated mice have smaller lesions than untreated mice. Four to eight C57BL/6 mice per experiment were injected with 1 × 106 L. amazonensis promastigotes in the right hind foot and treated with 200 mg/kg/day of imatinib or DMSO in their drinking water, starting 4 days before infection and continuing until sacrifice. Three separate experiments were performed; shown is a representative experiment containing 8 mice per group. Bars represent the increase in foot size compared to the uninfected foot (normalized to 1) ± SE. *, P < 0.05 by ANOVA. (B) arg−/− mice and (C) ablflox/flox/Tie2-Cre+ mice develop smaller lesions than WTLM when infected with 1 × 106 L. amazonensis promastigotes. Shown in panel B is a cohort of 5 mice per group in a representative experiment performed in duplicate using 4 to 5 mice per group. Shown in panel C is a cohort of 4 mice per group in a representative, duplicated experiment with 4 to 8 mice in each group. *, P < 0.05 by ANOVA. (D) Lesions in imatinib-treated mice contain fewer parasites than lesions in DMSO-treated mice (quantified by limiting dilution). Plotted is the parasite concentration in thousands at the termination of the experiment shown in panel A. *, P = 0.017 for DMSO versus imatinib-treated parasite burdens by two-sample t test. (E and F) arg−/− mice (E) and ablflox/flox/Tie2-Cre+ mice (labeled “abl−/−”) (F) have a lower parasite burden than WTLM. Shown is the final amount of L. amazonensis isolated from the infected foot from the WTLM versus the arg−/− experiment (E) and WTLM versus the ablflox/flox/Tie2-Cre+ experiment (F) from panels B and C, respectively. For panel E, P = 0.033 (*) for WTLM versus arg−/− parasite burdens, and for panel F, P = 0.017 (*) for WTLM versus ablflox/flox/Tie2-Cre+ parasite burdens by two-sample t test.