Polyamines shift expression of macrophage L-arginine metabolism related-genes during Leishmania amazonensis infection

Polyamines are molecules involved in macrophage activation and polarization in response to pathogens. The interaction with Leishmania promotes modulation of macrophage immune response to favor arginine deviation to polyamines production, leading to parasite survival. Polyamine levels are a potential modulator of growth factors, driving cells to proliferation, wound healing, oxidative stress, or regulating translation. Here, we investigate the impact of L-arginine and polyamines in the transcriptional regulation of genes involved in arginine metabolization and pro-inflammatory response to L. amazonensis in murine BALB/c macrophages. We found that supplementation with L-arginine is insufficient to modulate macrophage gene expression and infection. Polyamine supplementation altered nitric oxide synthase (Nos2) and nitric oxide (NO) production, as well as other macrophage enzymes. Putrescine supplementation increased transcript levels of polyamine metabolism-related genes Arginase 2 (Arg2), Spermidine synthase (SpdS), and Spermine synthase (SpmS) in both uninfected and L. amazonensis infected macrophages. Putrescine increased Nos2 expression without leading to NO production, while L-arginine plus spermine led to production of NO in uninfected macrophages. Besides, L-arginine supplementation reduced the levels of Il-1b during infection, and L-arginine or L-arginine plus putrescine increased Mcp1 at 24h of infection. The percentage of infected macrophages was lower after putrescine, spermidine, and spermine supplementation than L-arginine supplementation. Our data showed that the polyamines shift L-arginine-metabolism related-genes on BALB/c macrophages and affect infection by L. amazonensis.