Alta concentração de glicose aumenta o perfil M2 e reduz atividade microbicida de macrófagos desafiados com Encephalitozoon cuniculi

Resumo (EN)

Hyperglycemia, a marked alteration in diabetes, causes changes in the immune response and increases the susceptibility of diabetic individuals to infections. In macrophages cultured in high glucose concentration (HG), changes in metabolism, phenotype and phagocytic activity were identified, compromising their function as a primary line of defense. It was also reported that mice with streptozotocin-induced hyperglycemia had increased susceptibility to encephalitozoonosis, which was associated with a decrease in CD4+, B-1, B-2 T cells and decreased levels of IFN-γ. The aim of this study was to evaluate the effects of HG on the profile and activity of macrophages obtained from adherent peritoneal cells (APerC) challenged with the microsporidium E. cuniculi. APerC were cultured in RPMI medium supplemented with 10% fetal bovine serum (R10) or R10 with 30 mM glucose (R10HG30) and challenged with E. cuniculi spores at a concentration of 4
spores for each macrophage for 1, 3, 6 and 24 hours. After these periods, cell viability, median fluorescence intensity (MFI) of CD40 and CD206, fungal burden and production of Th1, Th2, Th17 cytokines were measured. Macrophages cultured in R10 medium and challenged with E. cuniculi for 1 hour and 3 hours showed an increase in the M2 profile and a decline in the M1/M2 ratio (1:1), with increased production of pro-inflammatory cytokines TNF-α and IL-6 and greater microbicidal activity (lower fungal burden) associated with increased NO production. In this same group, after 24 hours, there was an increase in M1 macrophages, a decrease in the M2 profile with an increase in the M1/M2 ratio (5:1), associated with an increase in the production of pro-inflammatory cytokines TNF-α, IL-6, IL- 17 and INF-γ. However, the microbicidal activity and NO production were like the R10HG30 group. When challenged with the pathogen for one hour and three hours, macrophages cultured with high glucose concentration demonstrated a macrophage profile like that observed in the treatment with R10, with a predominance of M2, associated with reduced microbicidal activity (higher fungal load compared to R10) and lower NO production. After 24 hours, although an increase in M1 macrophages was observed, M2 macrophages remained high, as well as a decline in the M1/M2 ratio (1:1). Corroborating this finding, cytokines with a mixed profile TNF-α, IL-6, IL-17, INF-γ and IL-10 were identified. It is concluded that the high glucose concentration directed macrophages to the M2 profile and reduced NO production and the microbicidal activity of M1 macrophages against E. cuniculii.