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Quantification of Intracellular Growth Inside Macrophages is a Fast and Reliable Method for Assessing the Virulence of Leishmania Parasites
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Polyamine-Enriched Exosomes from Leishmania donovani Drive Host Macrophage Polarization via Immunometabolism

Prince Sebastian1, Madhulika Namdeo1, Moodu Devender1

  • 1Department of Animal Biology, School of Life Sciences, University of Hyderabad, Hyderabad 500046, India.

ACS Infectious Diseases
|November 19, 2024
PubMed

Insights

Polyamines in Leishmania donovani exosomes are vital for parasite survival and drug resistance. These exosomes reprogram macrophages to an M2 state, promoting infection and creating an anti-inflammatory environment.

Area of Science:

  • * Parasitology
  • * Immunometabolism
  • * Molecular Biology

Background:

  • * Leishmania donovani (Ld) promastigotes release exosomes containing parasite molecules, influencing host-pathogen interactions.
  • * The role of unique metabolic components, particularly polyamines (PAs), within Ld-exosomes in modulating host immunometabolism remains unclear.

Purpose of the Study:

  • * To investigate the role of polyamines (PAs) in Ld-exosomes for parasite survival and fitness.
  • * To determine the impact of PAs-enriched Ld-exosomes on macrophage polarization and function.

Main Methods:

  • * Assessed the effect of PA inhibition/depletion on L. donovani growth and fitness.
  • * Analyzed macrophage uptake of Ld-exosomes.
  • * Evaluated macrophage polarization markers (Arginase-1, SLC3A2) and intracellular PA levels post-exosome internalization.

Main Results:

  • * Inhibition or depletion of PAs significantly impaired L. donovani growth, especially in drug-resistant strains.
  • * Macrophages efficiently internalized Ld-exosomes, enhancing phagocytic activity and infectivity.
  • * Internalized exosomes induced M2 macrophage polarization, evidenced by increased Arginase-1 activity and SLC3A2 expression, alongside elevated intracellular spermidine.

Conclusions:

  • * Polyamines are essential for L. donovani survival and fitness, particularly for drug-resistant parasites.
  • * Ld-exosomes promote parasite survival by inducing M2 macrophage polarization and contributing to the host's polyamine pool.
  • * These exosomes create a pro-parasitic, anti-inflammatory milieu within macrophages, facilitating infection establishment.
Keywords:
Anti-inflammatoryArginase-1ExosomesImmunometabolismMacrophage polarizationPolyamines

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