Avaliação da polarização de macrófagos de linhagem J774 na infecção por Leishmania braziliensis

Abstract

Cutaneous leishmaniasis represents a serious public health problem, with millions of new cases in Brazil and worldwide. It is a neglected infectious-parasitic disease caused by parasites of the genus Leishmania, with L. (Viannia) braziliensis being the main species associated with the cutaneous form in Brazil. Infection occurs after the bite of sandflies of the genus Lutzomyia, and its clinical manifestation depends on multiple factors, such as the Leishmania species involved, the immune response, and the metabolism of host cells. Among these cells, macrophages, as the main host cell, play a central role in the establishment and control of infection, standing out especially for their functional polarization toward the M1 (pro-inflammatory) and M2 (anti-inflammatory) profiles. This study investigated the effects of macrophage polarization on Leishmania braziliensis infection in J774 murine macrophages, analyzing parameters such as parasite load, cytokine production (TNF-α and IL-10), nitric oxide (NO) levels, arginase activity, and urea levels at 24 and 48 hours post-infection. It was observed that M2 macrophages were more permissive to infection and showed greater activation of the arginase pathway, while M1 macrophages produced higher levels of TNF-α and NO. However, even with an inflammatory profile, M1s were unable to eliminate the parasite during the observed period, suggesting that inflammation alone is not sufficient to control the infection. Furthermore, the metabolic reprogramming induced by L. braziliensis appears to favor parasite persistence over time. These findings reinforce the importance of understanding the interactions between metabolism and immunity in leishmaniasis and highlight the need for further studies that explore therapeutic targets capable of modulating this response. These results reinforce that M2 polarization favors parasite survival, while the M1 response, despite being more inflammatory, was unable to completely eliminate the infection during the analyzed periods, suggesting a possible role for parasite evasion mechanisms or the paradoxical effect of excess inflammation. Understanding the dynamics between cellular metabolism and immune response is crucial for developing more effective therapies.