@article{PAR00001878,
  title = {{SIR}2-{D}eficient {L}eishmania infantam induces a defined {IFN}-gamma/{IL}-10 pattern that correlates with protection},
  author = {{S}ilvestre, {R}icardo and {C}ordeiro {D}a {S}ilva, {A}. and {S}antarem, {N}. and {V}ergnes, {B}aptiste and {S}ereno, {D}enis and {O}uaissi, {A}li},
  editor = {},
  language = {{ENG}},
  abstract = {{T}he ability to manipulate the {L}eishmania genome to create genetically modified parasites by introducing or eliminating genes is considered a powerful alternative for developing a new generation vaccine against leishmaniasis. {P}reviously, we showed that the deletion of one allele of the {L}eishmania infantum silent information regulatory 2 ({L}i{SIR}2) locus was sufficient to dramatically affect amastigote axenic proliferation. {F}urthermore, {L}i{SIR}2 single knockout ({US}1112(+/+)) amastigotes were unable to replicate in vitro inside macrophages. {B}ecause this {L}. infuntunt mutant persisted in {BALB}/c mice for up to 6 wk but failed to establish an infection, we tested its ability to provide protection toward a virulent {L}. infuntum challenge. {S}trikingly, vaccination with a single i.p. injection of {L}i{SIR}2(+/+) single knockout elicits complete protection. {T}hus, vaccinated {BALB}/c mice showed a reversal of {T} cell anergy with specific anti-{L}eishinania cytotoxic activity and high levels of {NO} production. {M}oreover, vaccinated mice simultaneously generated specific anti-{L}eishmania {I}g{G} {A}b subclasses suggestive of both type {I} and type 2 responses. {A} strong correlation was found between the elimination of the parasites and an increased {L}eishmania-specific {IFN}-,gamma/{IL}-10 ratio. {T}herefore, we propose that the polarization to a high {IFN}-,gamma/low {IL}-10 ratio after challenge is a clear indicator of vaccine success. {F}urthermore these mutants, which presented attenuated virulence, represent a good model to understand the correlatives of protection in visceral leishmaniasis.},
  keywords = {},
  booktitle = {},
  journal = {{J}ournal of {I}mmunology},
  volume = {179},
  numero = {5},
  pages = {3161--3170},
  ISSN = {0022-1767},
  year = {2007},
  URL = {https://www.documentation.ird.fr/hor/{PAR}00001878},
}