modulate the host cell epigenome, including DNA methylation. This work aimed to explore the DNA methylation pattern in infected macrophages with , and . We performed a genome-wide methylation analysis in macrophages, cultured in presence/absence of interleukin 6 (IL-6) and infected with the three species for a period of 72hs. Upon 72hs infection, sample groups of - and -infected macrophages were treated with Glucantime and Amphotericin B for 48hs, respectively. Uninfected macrophages and macrophages treated with heat-killed were included as controls. Several CpG islands alterations were identified upon infection and among species. The methylome analysis showed that and clustered together separately from . The identified alterations were mainly associated with cytoskeleton organization. We also detected that the DNA methylation pattern of ten, six and eight CGIs for each aforementioned species slightly changed in a culture environment with IL-6, whereas treatment led to distinct DNA methylation profiles respect to untreated samples. Interestingly, some altered CGIs showed a re-establishment towards the control methylation pattern in (69%, 11 out of 16) and (36%, 4 out of 11). The identified alterations suggest a species-specific parasite/host interaction probably leading to gene expression regulation. The discovery of these methylation alterations addresses further functional studies and suggests them as potential therapeutic targets.