Leishmania major exacerbates infection with Leishmania infantum in BALB/c mice

Leishmania is an intracellular protozoan parasite that is transmitted by the bite of the phlebotomine sand fly. There are over 20 species of Leihsmania that infect humans causing a range of diseases from cutaneous - to systemic, potentially fatal infections. The geographic distribution of Leishmania major, responsible for cutaneous leishmaniasis, overlaps with several of the more virulent species of Leishmania. This study examined what effect previous exposure to L. major has on the outcome of infection with Leishmania infantum, the causative agent of highly pathogenic visceral leishmaniasis. The L. major immune response is well characterized with a strong cell-mediated immune response leading to resolution of disease, and protection against subsequent re-infection. A contrasting antibody-mediated immune response leads to disseminated disease. The immune response proteins (cytokine) profile, antibody titer and parasite burden were evaluated in the susceptible BALB/c mouse after L. infantum infection in either naïve mice or those previously infected with a low/self-healing dose of L. major. Using qPCR, expression of the immune protein Interleukin 4, associated with increased antibody response, was found to be significantly increased in mice previously exposed to L. major over controls . Exacerbated disease, with a notably higher parasite burden, was observed in the L. major exposed mice compared to those infected with L. infantum only. Cross-reactive antibodies were seen in both groups of infected mice regardless of their immune history. We speculate cross-reactive antibodies may be playing a role in augmenting visceral disease in mice with immunological memory to L. major