Overall, the present study showed that Leishmania subverts the macrophage–miRNA profile, altering miR-294, miR-301b, and miR-410 expression and the transcripts of the target genes Cat2/Slc7a2, Cat1/Slc7a12 Nos2, and Tnfa, building a complex network of miRNAs–mRNAs modulated during the recognition and activation of macrophages, leading to an infection outcome. Here, TNF is linked to infection.