Listeria monocytogenes as a Short-Lived Delivery System for the Induction of Type 1 Cell-Mediated Immunity against the p36/LACK Antigen of Leishmania major

Listeria monocytogeneshas been used as an experimental live vector for the induction of CD8-mediated immune responses in various viral and tumoral experimental models. Susceptibility of BALB/c mice toLeishmania majorinfection has been correlated to the preferential development of Th2 CD4 T cells through an early production of interleukin 4 (IL-4) by a restricted population of CD4 T cells which react to a single parasite antigen, LACK (stands forLeishmaniahomologue of receptors for activated C kinase). Experimental vaccination with LACK can redirect the differentiation of CD4+T cells towards the Th1 pathway if LACK is coadministrated with IL-12. As IL-12 is known to be induced byL. monocytogenes, we have tested the ability of a recombinant attenuatedactAmutantL. monocytogenesstrain expressing LACK to induce the development of LACK-specific Th1 cells in both B10.D2 and BALB/c mice, which are resistant and susceptible toL. major, respectively. After a single injection of LACK-expressingL. monocytogenes, IL-12/p40 transcripts showed a rapid burst, and peaks of gamma interferon (IFN-γ)-secreting LACK-specific Th1 cells were detected around day 5 in the spleens and livers of mice of both strains. These primed IFN-γ-secreting LACK-reactive T cells were not detected ex vivo after day 7 of immunization but could be recruited and detected 15 days later in the draining lymph node after anL. majorfootpad challenge. Although immunization of BALB/c mice with LACK-expressingL. monocytogenesdid not change the course of the infection withL. major, immunized B10.D2 mice exhibited significantly smaller lesions than nonimmunized controls. Thus, our results demonstrate that, in addition of its recognized use for the induction of effector CD8 T cells,L. monocytogenescan also be used as a live recombinant vector to favor the development of potentially protective IFN-γ-secreting Th1 CD4 T lymphocytes.