biostudies-literatureVargas DANIAID NIH HHSFIC NIH HHSWellcome Trust1242727https://www.ebi.ac.uk/biostudies/studies/S-EPMC10795579biostudies-literatureUnknown2Host cell functions that participate in the pharmacokinetics and pharmacodynamics (PK/PD) of drugs against intracellular pathogen infections are critical for drug efficacy. In this study, we investigated whether macrophage mechanisms of xenobiotic detoxification contribute to the elimination of intracellular <i>Leishmania</i> upon exposure to pentavalent antimonials (Sb^V). Primary macrophages from patients with cutaneous leishmaniasis (CL) (n=6) were exposed <i>ex vivo</i> to <i>L. V. panamensis</i> infection and Sb^V, and transcriptomes were generated. Seven metallothionein (MT) genes, potent scavengers of heavy metals and central elements of the mammalian cell machinery for xenobiotic detoxification, were within the top 20 up-regulated genes. To functionally validateFrontiers in parasitologyMacrophage metallothioneins participate in the antileishmanial activity of antimonials.PMC10795579107595/Z/15/ZD43 TW006589R01 AI104823U19 AI129910Zilberstein DKoren RNGomez MAGregory DJEl-Sayed NMBelew ATVargas DAfalseMacrophage metallothioneins participate in the antileishmanial activity of antimonials.Host cell functions that participate in the pharmacokinetics and pharmacodynamics (PK/PD) of drugs against intracellular pathogen infections are critical for drug efficacy. In this study, we investigated whether macrophage mechanisms of xenobiotic detoxification contribute to the elimination of intracellular <i>Leishmania</i> upon exposure to pentavalent antimonials (Sb^V). Primary macrophages from patients with cutaneous leishmaniasis (CL) (n=6) were exposed <i>ex vivo</i> to <i>L. V. panamensis</i> infection and Sb^V, and transcriptomes were generated. Seven metallothionein (MT) genes, potent scavengers of heavy metals and central elements of the mammalian cell machinery for xenobiotic detoxification, were within the top 20 up-regulated genes. To functionally validate2023-01-01T00:00:00Z20232026-06-02T06:11:20.163Z2024-10-16T00:11:48.606ZS-EPMC107955793823942910.3389/fpara.2023.1242727