O impacto de distintas cepas de Plasmodium berghei na resposta de macrófagos peritoneais pré-tratados com ômega-3 rico em DHA

Abstract

Malaria remains a major global public health concern and is characterized by an intense inflammatory response that, although essential for controlling infection, also contributes to the development of severe disease. In this context, compounds with immunomodulatory properties, such as docosahexaenoic acid (DHA), have been investigated as potential adjuvant therapeutic strategies. Previous studies conducted by our research group demonstrated that supplementation with DHA-rich omega-3 attenuates brain and lung damage induced by Plasmodium berghei ANKA (PbA) infection but does not exert the same effect during Plasmodium berghei NK65 (PbN) infection. Therefore, the present study aimed to evaluate the impact of the PbA and PbN strains on the modulation of the functional response of peritoneal macrophages previously treated with DHA-rich omega-3. Peritoneal macrophages obtained from BALB/c mice were pretreated with different DHA concentrations and subsequently incubated with erythrocytes infected with PbA or PbN for 6 and 12 hours. The production of the cytokines IFN-γ, IL-6, TNF-α, and IL-10, nitric oxide (NO), hydrogen peroxide (H2O2), lipid body formation, and macrophage phagocytic capacity were evaluated. The results demonstrated that pretreatment with DHA-rich omega-3 did not significantly alter the production of cytokines, reactive nitrogen and oxygen species, or lipid body formation following incubation with PbA or PbN infected erythrocytes. However, an increase in the phagocytic capacity of treated macrophages was observed, particularly at the highest DHA concentrations. Furthermore, differences in the functional response of macrophages to the two P. berghei strains were identified, suggesting that parasite-specific characteristics influence the response to treatment. Overall, the results indicate that the main direct effect of DHA-rich omega-3 on macrophages is associated with enhanced phagocytic capacity, where as its anti-inflammatory effects observed in experimental in vivo models are likely dependent on the interaction among different cell populations, inflammatory mediators, and the tissue microenvironment.