Antimony resistance associated with persistence of Leishmania (Leishmania) infantum infection in macrophages

Parasitol Res. 2021 Aug;120(8):2959-2964. doi: 10.1007/s00436-021-07231-7. Epub 2021 Jul 17.

Abstract

Visceral leishmaniasis is a severe disease caused by protozoan parasites that include Leishmania (L.) infantum. The disease is established when parasites subvert the immune response of the host. Notably, chemotherapy-based use of antimonial compounds can partially alleviate disease burden. Unfortunately, the resistance to drug treatments is increasing in areas endemic to the disease. In this report, we investigated immune responses within macrophages infected with antimony-resistant L. infantum isolates from patients with a relapse in the disease. Results revealed that antimony-resistant parasites persist in the first 24 h of infection. Activation of macrophage or blocking of thiol production during infection shows enhanced clearance of parasites, which is coordinately associated with increased production of pro-inflammatory cytokines. Taken together, these results suggest that the mechanism of antimony resistance in L. infantum isolates may be related to a decrease in macrophage microbicidal functions.

Keywords: Leishmania infantum; Macrophages; Meglumine antimoniate; Visceral leishmaniasis.

MeSH terms

  • Antimony* / pharmacology
  • Drug Resistance*
  • Humans
  • Leishmania infantum* / drug effects
  • Leishmaniasis / drug therapy
  • Leishmaniasis / immunology*
  • Macrophages / immunology*
  • Macrophages / parasitology
  • Meglumine Antimoniate

Substances

  • Meglumine Antimoniate
  • Antimony