Resumo:
INTRODUCTION: Leishmaniasis is a disease caused by protozoa of the genus Leishmania, belonging to the Trypanosomatidae family, and remains a significant public health problem in several regions of the world, including Brazil. Leishmania amazonensis is the main species associated with diffuse cutaneous leishmaniasis (DCL), although it is also involved in cases of localized cutaneous leishmaniasis (LCL). Our group has been investigating inflammatory mechanisms triggered by surface glycoconjugates of promastigotes, such as lipophosphoglycan (LPG) and other phosphoglycans (PPGs). Strategies based on parasites deficient in these molecules have been fundamental to understanding their role during infection. OBJECTIVES: This study aimed to investigate the contribution of the lpg2 gene to the early stages of the host-parasite interaction and the survival of L. amazonensis in murine macrophages. METHODS: Bone marrow-derived macrophages from C57BL/6 mice were infected with wild-type (WT) or lpg2-deficient (Δlpg2) L. amazonensis promastigotes. A 5:1 (parasite: macrophage) ratio was used for the assays. RESULTS: Δlpg2 parasites showed a significant reduction in intracellular parasite load and viability compared to the WT strain. In the early moments of infection, Δlpg2 parasites preferentially entered through the cell body, whereas WT parasites predominantly interacted via the flagellar tip. Mutants also exhibited greater colocalization with acidified intracellular compartments and increased production of reactive oxygen species (ROS), with no significant differences in nitrite levels, an indirect marker of nitric oxide (NO) production. CONCLUSION: The results indicate that the lpg2 gene of L. amazonensis is crucial for the success of infection in C57BL/6 macrophages, since its absence compromises parasite viability during the interaction with the host cell.
