Deletion of MIF gene from live attenuated LdCen−/− parasites enhances protective CD4+ T cell immunity

Abstract Vaccination with live attenuated Leishmania parasites such as centrin deleted Leishmania donovani ( LdCen −/− ) against visceral leishmaniasis has been reported extensively. The protection induced by LdCen −/− parasites was mediated by both CD4 + and CD8 + T cells. While the host immune mediators of protection are known, parasite determinants that affect the CD4 + and CD8 + T cell populations remain unknown. Parasite encoded inflammatory cytokine MIF has been shown to modulate the T cell differentiation characteristics by altering the inflammation induced apoptosis during contraction phase in experimental infections with Leishmania or Plasmodium . Neutralization of parasite encoded MIF either by antibodies or gene deletion conferred protection in Plasmodium and Leishmania studies. We investigated if the immunogenicity and protection induced by LdCen −/− parasites is affected by deleting MIF genes from this vaccine strain. Our results showed that LdCen −/− MIF −/− immunized group presented higher percentage of CD4 + and CD8 + central memory T cells, increased CD8 + T cell proliferation after challenge compared to LdCen −/− immunization. LdCen −/− MIF −/− immunized group presented elevated production of IFN-γ + and TNF-α + CD4 + T cells concomitant with a reduced parasite load in spleen and liver compared to LdCen −/− group following challenge with L. infantum . Our results demonstrate the role of parasite induced factors involved in protection and long-term immunity of vaccines against VL.