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Iron trafficking in patients with Indian Post kala-azar dermal leishmaniasis

Aishwarya Dighal1, Debanjan Mukhopadhyay1, Ritika Sengupta1

  • 1Dept. of Pharmacology, Institute of Postgraduate Medical Education and Research, Kolkata, India.

Plos Neglected Tropical Diseases
|February 6, 2020
PubMed
Abstract

Insights

Iron levels in monocytes/macrophages are elevated in Post Kala-azar Dermal Leishmaniasis (PKDL) due to increased iron uptake, despite higher iron export. This creates a pro-parasitic environment, suggesting new therapeutic strategies to restrict iron availability to the parasite.

Area of Science:

  • Immunology
  • Infectious Diseases
  • Trace Element Metabolism

Background:

  • Iron is crucial in infections, benefiting pathogens but also aiding host defense.
  • Its role in visceral leishmaniasis is known, but less so in Post Kala-azar Dermal Leishmaniasis (PKDL).
  • This study investigates iron status in PKDL monocytes/macrophages.

Purpose of the Study:

  • To determine the iron status within monocytes/macrophages in Post Kala-azar Dermal Leishmaniasis (PKDL) cases.
  • To understand iron transport mechanisms in PKDL lesions.
  • To identify potential therapeutic targets for PKDL.

Main Methods:

  • Flow cytometry and ELISA measured intramonocytic labile iron pool (LIP), CD163, CD71, and soluble CD163 in monocytes.
  • Prussian blue staining assessed Fe3+ in lesions; qPCR quantified parasite load.
  • Droplet digital PCR analyzed mRNA expression of iron-related genes (TfR, CD163, DMT-1, Lcn-2, HO-1, Ferritin, NRAMP-1, Fpn-1).

Main Results:

  • PKDL monocytes showed elevated CD71, CD163, and soluble CD163.
  • Lesional mRNA expression of TfR, CD163, DMT1, and Lcn-2 was increased.
  • Elevated LIP correlated with increased ferritin and HO-1 mRNA, and higher expression of iron exporters NRAMP-1 and Fpn-1.

Conclusions:

  • Increased iron influx via TfR, CD163, DMT-1, and Lcn-2 likely contributes to elevated LIP in PKDL.
  • Enhanced NRAMP-1 and Fpn-1 expression contradicts the typical macrophage phenotype, suggesting a pro-parasitic environment.
  • Targeting iron availability to parasites may offer novel PKDL treatment strategies.

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