The drug resistance mechanisms in Leishmania donovani are independent of immunosuppression. (September 2021)

• Record Type: Journal Article
• Authors: Saha, Baibaswata; Pai, Kalpana; Sundar, Shyam; Bhattacharyya, Maitree; Bodhale, Neelam Prakash
• Is Part Of: Cytokine. Volume 145(2021)
• Publication Date: 2021-09
• Subjects: Leishmania -- Drug-resistance -- Mechanisms; Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2020.155300
• Languages: English
• ISSNs: 1043-4666

Abstract

Abstract: The protozoan parasite L. donovani resides inside macrophages as amastigotes and inflicts a potentially lethal disease visceral leishmaniasis (VL). Due to absence of a vaccine, chemotherapy with antimonials, amphotericin B, miltefosine or paromomycin remains the only option for treating VL. Prolonged treatment with a single drug resulted in parasite strains resistant to each of these drugs. As immuno-suppression characterizes the disease, we examined whether eliciting immunosuppressive cytokines is a mechanism of manifestation of drug-resistance. We infected BALB/c mice with the clinical isolates of L. donovani - BHU1066 (sensitive), NS2 (antimony-resistant), BHU1064 (miltefosine-resistant), BHU919 (Amphotericin B-resistant) and BHU1020 (paromomycin-resistant)- from the respective drug-unresponsive patients and assessed splenic parasite load and production of pro-inflammatory and anti-inflammatory cytokines. Although the splenic parasite loads in the drug-resistant L. donovani -infected BALB/c mice were higher than that observed in the drug-sensitive parasites-infected mice, the cytokine profiles were not significantly different between these two sets of mice. The drug-resistance in L. donovani results from innate drug modulation but perhaps not from host immune-suppressive cytokines.