Imprinting of BALB/c mice with low Leishmania infantum parasite dose markedly protects spleen against high-dose challenge

Abstract In this study, we investigated in the BALB/c model, the dose-dependent protective potential of previous infection with Leishmania infantum parasites, against a high-dose challenge and showed for the first time that low-dose imprinting conferred substantial spleen resistance. Mice were immunized for 1 month or 5 months by IV route with parasite inocula ranging from 10 4 to 10 7 and from 10 3 to 10 5 , respectively, and challenged for 1 month with 3 × 10 7 parasites. Liver protection was directly proportional to the parasite dose used for infection and reached 90–95% whereas, only low doses (≤10 5 ) protected spleen. Maximal spleen resistance (80%) was reached in mice infected for 5 months with 10 5 parasites. In most cases, protection was accompanied in spleen, by restored in vitro responses to Leishmania antigens. Analysis of anti L. infantum isotype responses and in vitro antigen-induced cytokine production, indicated that the acquired protection was irrespective of a Th1/Th2 imbalance.