Immune and pathological parameters in BALB/c mice infected with low and high-dose of Leishmania amazonensis.

CARGNELUTTI D.E.; SANCHEZ M.V.; MOREA G.; GARCÍA BUSTOS M.F.; SALOMÓN M.C.; SCODELLER E.A.; GEA S.

Recife

Congreso; V World Leishmania Congress; 2013

Oswaldo Cruz Foundation

Human leishmaniasis is a neglected endemic disease caused by more than 20 Leishmania species and with a broad spectrum of clinical manifestations. Leishmania amazonensis, an etiological agent of localized and diffuse cutaneous leishmaniasis in South America also cause severe pathology in BALB/c mice displaying persistent lesions. In this study, we comparatively investigated the impact of infection in immune response and tissue damage using BALB/c mice infected with low (103) and high (106) number of L. amazonensis metacyclic promastigotes (MHOM/VE/84/MEL). BALB/c mice (eight to nine week old; n: 5 per group) were infected with 103or 106parasites into the dermis of the footpad and the evolution of infection was assessed until day 70 post-infection. Uninfected mice were used as controls. The appearance of lesions in mice infected with 103 parasites was delayed compared to mice infected with 106 parasites. The study of the humoral immune response revealed the induction of specific IgG antibodies, IgG1 and IgG2a isotypes.  Mice infected with 103 parasites presented lower levels of reactivity of IgG, IgG1 and IgG2a antibodies than mice infected with 106 promastigotes at 70 days post infection. However, the relation between the two antibody isotypes was similar in the two experimental conditions. These results indirectly suggest a simultaneous activation of Th1 and Th2                    T lymphocytes. In addition, the low production of nitric oxide in splenocyte culture supernatants (about 3.5 mM) suggests a reduction in inducible nitric oxide synthase (iNOS) activation. These results were associated with high splenic index and lesion histological score (more than 20) with inflammatory infiltrate at the site of infection. Thus, these latter findings did not reveal significant differences between the experimental groups. In summary, our data show that the appearance of lesions in mice infected with low dose of parasites was delayed compared to mice infected with high dose of Leishmania. However, low-dose infection did not result in changes neither the lesion susceptibility nor histological parameters de­scribed for subcutaneous infection with high numbers of parasites. We postulated that L. amazonensis has developed strategies to escape from host defense favoring the establishment and success of the infection.