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Evaluating LeishPepThera (PepA) as an immuno-therapeutic for Leishmania major infection

Shweta Khandibharad1, Shailza Singh1,2

  • 1Systems Medicine Laboratory, BRIC - National Centre for Cell Science, NCCS Complex, Ganeshkhind, SPPU Campus, Pune 411007, India.

Iscience
|December 16, 2025
PubMed

Insights

A novel peptide therapy, Peptide A (PepA), effectively targets SHP-1 to combat cutaneous leishmaniasis. This approach rebalances immune signaling, reduces parasite load, and offers a promising new treatment for CL.

Area of Science:

  • Immunology
  • Parasitology
  • Drug Discovery

Background:

  • Cutaneous leishmaniasis (CL) pathogenesis involves immune dysregulation, specifically the Interleukin-12 (IL-12) and Interleukin-10 (IL-10) axis.
  • Src homology 2 domain-containing protein tyrosine phosphatase (SHP-1) activity promotes parasite survival by modulating this immune axis.

Purpose of the Study:

  • To design and evaluate AI-driven therapeutic peptides targeting SHP-1 for CL treatment.
  • To investigate the immunomodulatory effects of SHP-1 inhibiting peptides in a *Leishmania major* infection model.

Main Methods:

  • Artificial intelligence was used to design peptides targeting SHP-1.
  • Peptide A (PepA) was evaluated in a *Leishmania major* infection model.
  • Assessed SHP-1 inhibition, NFAT5 translocation, nitric oxide (NO) production, macrophage polarization, cytokine profiles (IL-12, IL-10), and parasite load.

Main Results:

  • Peptide A demonstrated potent SHP-1 inhibition, enhanced NFAT5 translocation, and increased NO production via iNOS upregulation.
  • PepA induced M1 macrophages, restored IL-12 levels, suppressed IL-10 expression, and significantly reduced parasite burden.
  • The peptide rebalanced host immune signaling pathways crucial for parasite clearance.

Conclusions:

  • Peptide A (LeishPepThera) is a promising immunotherapeutic candidate for cutaneous leishmaniasis.
  • Targeting SHP-1 with PepA offers a novel strategy for rebalancing host immunity and clearing *Leishmania* parasites.

Keywords:
Cell biologyImmunology

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