Camundongos C57BL/6 deficientes nas citocinas IL-12 e IL-23 vacinados com antígeno do parasita desenvolvem resistência a infecção por Leishmania amazonensis

Abstract

Protozoa of the genus Leishmania are intracellular parasites and may cause diverse clinical forms of leishmaniasis, including cutaneous, diffuse cutaneous, mucocutaneous and visceral leishmaniasis. Infection with L. major in mice indicates that a protective immune response is achieved when Th1 cells are developed. Thus, adoptive or vaccine-induced protection against leishmaniasis is largely dependent on cell mediated type 1 immune response and IL-12-driven IFN- production. Surprisingly, our data showed that IL-12/23p40-/- mice could be vaccinated against L. amazonensis and were able to produce limited amounts of IFN-. The aim of this study was to evaluate the possible IL-12-indepent mechanisms involving different cell types, such as CD8+ T cells, NK , NKT cells and DC and other cytokines that replace the function of IL-12, such as IL-27 and IL-18 in protection against L. amazonensis in vaccinated mice. IL-12/23p40-/- mice were immunized with two inoculations, seven days apart, of Leishvacin (Biobrás, Montes Claros, MG, Brazil) plus Corynebacterium parvum as adjuvant. Twenty-eight days later, animals received a booster and were infected with L. amazonensis seven days later. CD8+, NK and NKT cells were depleted and IFN- was neutralizated by treatment of vaccinated mice by treatment with monoclonal antibodies before and after L. amazonensis infection. Non vaccinated infected mice were used as a control group. Infection was followed for 8 weeks. It was verified that CD8+ T cells are not required for vaccine-induced immunity against L. amazonensis infection in these mice. IL-27 levels were similar between knockout vaccinated and wt mice. NK1.1-depleted vaccinated group and IFN--neutralizated group developed larger lesions when compared to the vaccinated group and similar lesions compared with control group. The parasite burdens in the NK1.1-depleted vaccinated and IFN--neutralized group were similar to control group. In addition, the control group showed reduction of NKT cells in spleen and lymph node compared with the vaccinated group, suggesting a role for NKT cells in control of lesions. Interestingly, the vaccinated group had higher frequency of dendritic cells in the lesion. Such results suggest that NKT cells play an important role in L. amazonensis vaccination in IL12/23p40-/- animals contributing to lesion control.