Listeria monocytogenes Inoculation Protects Mice against Blood-Stage Plasmodium yoelii Infection

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Listeria monocytogenes (Lm) has been used as the adjuvant or vector for tumor and viral vaccine for its capability of eliciting all aspects of cell-mediated immunity including T cell activation and interferon-gamma (IFN-γ) production. These effector components play critical roles in the protection against Plasmodium infection in both human malaria and mouse models. Therefore, immune response induced by Lm infection may benefit the defense against malaria. To test this hypothesis, we employed blood-stage Plasmodium yoelii (PyL) infected mice and challenged them with Lm. C57BL/6 and BALB/c mice that are sensitive to PyL infection were used in experiments. These two strains are resistant and sensitive, respectively, to Lm infection. The outcomes of double infection with PyL and Lm and the changes of immune response were investigated. We found that live Lm inoculation inhibited PyL multiplication in both C57BL/6 and BALB/c mice. Lm inoculation increased production of IFN-γ, infiltration of CD11b-positive macrophages and generation of nitric oxide in the spleen of C57BL/6 mice at day 5 after parasite infection. Both CD4- and CD8- positive T cells contributed to IFN-γ production induced by Lm inoculation in PyL-infected mice. The protective effect of Lm against PyL infection depended on the viability of the bacteria. Live Lm, rather than heat-killed Lm, stimulated early IFN-γ production which provided essential cytokine environment for the development of Th1 response in PyL-infected mice. Our data show for the first time that Lm inoculation has protective effect against blood-stage murine malaria, which provides a new clue for enhancing anti-Plasmodium immunity.