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Cytokine. 2021 Sep;145:155300. doi: 10.1016/j.cyto.2020.155300. Epub 2020 Sep 23.

The drug resistance mechanisms in Leishmania donovani are independent of immunosuppression.

Cytokine

Baibaswata Saha, Kalpana Pai, Shyam Sundar, Maitree Bhattacharyya, Neelam Prakash Bodhale

Affiliations

  1. Centre of Advanced Study, Department of Zoology, Savitribai Phule Pune University, Pune 411007, India.
  2. Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, India.
  3. Jagadis Bose National Science Talent Search, Kolkata 700107, India.
  4. Jagadis Bose National Science Talent Search, Kolkata 700107, India; National Centre for Cell Science, Ganeshkhind, Pune 411007, India. Electronic address: [email protected].

PMID: 32978033 DOI: 10.1016/j.cyto.2020.155300

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.

Copyright © 2020 Elsevier Ltd. All rights reserved.

Keywords: Drug-resistance; Leishmania; Mechanisms

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