Characterization of Sv129 Mice as a Susceptible Model to Leishmania amazonensis

Abstract

Leishmaniasis is a complex of neglected diseases caused by parasites of the genus Leishmania , such as Leishmania (Leishmania) amazonensis , the ethiologic agent of diffuse cutaneous leishmaniasis in Brazil. In this work, we investigated a new experimental model of infection for L. amazonensis : the Sv129 mouse. First, we subcutaneously infected Sv129 mice with 2 × 10 5 or 2 × 10 6 L. amazonensis parasites of the Josefa strain. A progressive lesion developed for both inoculation doses, showing that Sv129 mice are susceptible, independent of parasite dose. We next investigated the mechanisms associated with the pathogenesis of infection. We did not observe an increase of frequency of interferon-gamma (IFN- γ)-producing CD4 + and CD8 + T cells, a phenotype similar to that seen in BALB/c mice. There was an increased of frequency and number of IL-17-producing γδ (gamma-delta) T cells in infected Sv129 mice compared to naïve SV129 and an increased frequency of this population compared to infected BALB/c mice. In addition, Sv129 mice presented high levels of both IgG1 and IgG2a, suggesting a mixed Th1 and Th2 response with a skew toward IgG1 production based on IgG1/IgG2a ratio. Susceptibility of the Sv129 mice was further confirmed with the use of another strain of L. amazonensis , LTB0016. In this work, we characterized the Sv129 mice as a new model of susceptibility to Leishmania amazonensis infection, during infection there was controlled IFN-γ production by CD4 + or CD8 + T cells and induced IL-17 production by γδ T cells.

IL-17A/IFN-γ producing γδ T cell functional dichotomy impacts cutaneous leishmaniasis in mice

“…We previously showed that L.amazonensis infection induces an increase of IL-17A-producing γδ T cells in Sv129 mice 31 . However, their precise contribution to the IL-17A response in L. amazonensis infection was not known before the present study.…”

“…We have previously demonstrated that L. amazonensis infection of Sv129 mice fails to induce expansion of IFN-γ producing CD4 and CD8 T cells, but it triggers the expansion of IL-17A producing γδ T cells 31 . To determine the main source of IL-17A in L. amazonensis infection, we performed a flow cytometry analysis of the draining popliteal lymph node of mice infected in the footpad.…”

“…IL-17 + cells have been associated with DCL caused by L. amazonensis 23 , but the underlying main source of this cytokine has not yet been revealed. Interestingly, in human leishmaniasis, the clinical presentations mediated by L. amazonensis, L. major and L. braziliensis infection associate with increased γδ T cells 24-30. ; and in experimental leishmaniasis, L. amazonensis infection in susceptible Sv129 mice induces the expansion of IL-17A producing γδ T cells, but not Th17 cells 31 . IL-17 production by γδ T cells protects against fungi 32 and bacteria, such as Listeria or Staphylococcus 33 .…”

“…Interestingly, in human leishmaniasis, the clinical presentations mediated by L. amazonensis , L. major and L. braziliensis infection associate with increased γδ T cells 24–30 . ; and in experimental leishmaniasis, L. amazonensis infection in susceptible Sv129 mice induces the expansion of IL-17A producing γδ T cells, but not Th17 cells 31 .…”

MPLA and AddaVax® Adjuvants Fail to Promote Intramuscular LaAg Vaccine Protectiveness against Experimental Cutaneous Leishmaniasis

“…However, it is worth mentioning that, at the peak phase of infection until the end of the experiment, the number of parasites was similar. Recently, dos-Santos et al [33] reported that, during infection with the L. amazonensis Josefa strain in Sv129 mice, although there was a difference in the time of lesion development between inoculums of 2 × 10 5 and 2 × 10 6 , the lesions were equal at the end of 16 weeks of infection and there was not a difference in the parasite load at the end. Thus, the inoculation dose can greatly influence the profile of Leishmania infection.…”