Comparação do perfil dos macrófagos oriundos de camundongos BALB/c infectados com Leishmania (V.) braziliensis e Leishmania (L.) major

Abstract

Infection with Leishmania sp. produces a varied spectrum of clinical manifestations in humans and animals. Studies using animal models are valuable in helping to understand the parasite-host relationship. BALB/c mice are susceptible to infection by most Leishmania species, however they are considered resistant to L.braziliensis, as they present small lesions that regress in a few weeks. The macrophage is the main host cell of the parasite and also the final effector cell, capable of controlling the infection. Resistance to infection correlates with a Th1 response involving macrophages with an M1 phenotype, while susceptibility to Th2-M2, this dichotomy being well evidenced especially for infection with L. major. The objective of this study was to comparatively evaluate the profile of peritoneal macrophages in BALB/c mice infected with L. braziliensis and L. major in the ear. Peritoneal macrophages were analyzed at three different times of infection 7, 15 and 21 days after infection (DPI). Our results showed that animals infected with L. braziliensis are able to fully control the lesion at 21 DPI, peaking at 15 DPI, as expected. Animals infected with L. major developed lesions that progressively enlarged. BALB/c macrophages infected with L. braziliensis showed the ability to control the number of amastigotes when infected in vitro and increased NO production at 15 DPI. We analyzed the subpopulations of large peritoneal macrophages (LPM) and small peritoneal macrophages (SPM) and observed that infection with L. braziliensis promoted a higher frequency of M1 markers, especially at 7-15 DPI when compared to L. major. The higher frequency of LPM with M1 phenotype up to 15 DPI and the production of NO may have contributed to the resolution of the lesion and the resistance profile of BALB/c mice infected with L. braziliensis. In the same way, the SPM that correspond to the smallest population, also showed an M1 profile. Overall, these results agree with the idea that resistance to L.braziliensis infection correlates with the induction of classically activated macrophages (M1), while infection with L.major correlates with the presence of alternatively activated macrophages (M2) and uncontrolled infection.