Schematic representation of <i>L</i>. <i>(L</i>.<i>) amazonensis</i> promastigote and amastigote NO production in the infection context.

<p>In <i>L</i>. <i>(L</i>.<i>) amazonensis</i>, the AAP3 transporter takes up L-arginine, and this amino acid is metabolized by arginase into ornithine to produce polyamines or via NOS-like to produce NO. <i>La</i>-WT-infected macrophages increase the activity of the polyamine pathway, increasing the expression of the L-arginine transporter from the host (CAT2B) and parasite (AAP3), arginase1 (host) and parasite-arginase to metabolizing L-arginine to produce polyamines, consequently sustaining the basal level of NOS2 expression and NO production. Indeed, the <i>La</i>-WT amastigote differentiation induces NOS-like expression and NO production, higher levels than promastigotes, but lower than those produced by macrophages. The lack of arginase activity in promastigotes increases the L-arginine levels, even that the reduction in AAP3 expression, inducing the expression of NOS-like, NO and citrulline production. The <i>La</i>-arg^—infected macrophages present lower levels of CAT2B and AAP3, which could reduce L-arginine uptake, and lower the levels of arginase 1 and polyamine production compared with <i>La</i>-WT infection allowing the increase in NOS2 expression and NO production, reducing infectivity. In addition, the <i>La</i>-arg^- amastigote differentiation induces NOS-like expression but not AAP3 expression and L-arginine uptake sufficient to increase NO production compared with <i>La</i>-WT promastigotes. PV: parasitophorous vacuole.