SIR2-Deficient Leishmania infantum Induces a Defined IFN-γ/IL-10 Pattern That Correlates with Protection
作者： Ricardo Silvestre , Anabela Cordeiro-Da-Silva , Nuno Santarém , Baptiste Vergnes , Denis Sereno
DOI: 10.4049/JIMMUNOL.179.5.3161
关键词:
摘要: The ability to manipulate the Leishmania genome create genetically modified parasites by introducing or eliminating genes is considered a powerful alternative for developing new generation vaccine against leishmaniasis. Previously, we showed that deletion of one allele infantum silent information regulatory 2 (LiSIR2) locus was sufficient dramatically affect amastigote axenic proliferation. Furthermore, LiSIR2 single knockout (LiSIR2(+/-)) amastigotes were unable replicate in vitro inside macrophages. Because this L. mutant persisted BALB/c mice up 6 wk but failed establish an infection, tested its provide protection toward virulent challenge. Strikingly, vaccination with i.p. injection LiSIR2(+/-) elicits complete protection. Thus, vaccinated reversal T cell anergy specific anti-Leishmania cytotoxic activity and high levels NO production. Moreover, simultaneously generated IgG Ab subclasses suggestive both type 1 responses. A strong correlation found between elimination increased Leishmania-specific IFN-gamma/IL-10 ratio. Therefore, propose polarization IFN-gamma/low IL-10 ratio after challenge clear indicator success. Furthermore these mutants, which presented attenuated virulence, represent good model understand correlatives visceral
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