Interplay of human macrophage response and natural resistance of L. (V.) panamensis to pentavalent antimony

This investigation provides evidence of the significant differential macrophage response to ex vivo infection with clinical strains of L. (V.) panamensis naturally resistant (zymodeme 2.3) or sensitive (zymodeme 2.2) to antimonial drug, and the distinct effect of this drug on the activation profile of macrophages. Transcriptome analysis of monocyte-derived macrophages from healthy donors, infected and exposed to antimony, revealed significant proinflammatory activation by zym 2.3 strains compared with zym 2.2 strains. Furthermore, in the presence of antimony, macrophages infected with zym 2.3 strains, but not with zym 2.2 strains, modulated the inflammatory profile elicited by infection to an anti-inflammatory profile. Notably, macrophages infected with zym 2.3 strains exhibited elevated expression of genes associated with proinflammatory regulation as well as transporters compared to those infected with zym 2.2 strains. Remarkably, the majority of these pathways remained upregulated even in the presence of the strong modulatory effect of antimonial drug.