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Localization and RNA Interference-Driven Inhibition of a Brugia malayi-Encoded Interleukin-5 Receptor Binding Protein

Rojelio Mejia1, Sasisekhar Bennuru1, Yelena Oksov2

  • 1Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA.

Infection and Immunity
|April 25, 2022
PubMed

Insights

Researchers identified a Brugia malayi protein that inhibits human IL-5R binding, offering a potential target for filarial worm therapies. This parasite-encoded antagonist may locally disrupt host immune responses.

Area of Science:

  • Parasitology
  • Immunology
  • Molecular Biology

Background:

  • Brugia malayi is a filarial worm responsible for lymphatic filariasis.
  • Interleukin-5 (IL-5) plays a crucial role in host innate immunity, particularly in eosinophil activation.
  • Parasitic worms often employ strategies to evade or manipulate host immune responses.

Purpose of the Study:

  • To identify and characterize a molecule from Brugia malayi that interferes with human IL-5 signaling.
  • To investigate the localization and function of this molecule in the parasite.
  • To assess the potential of this molecule as a therapeutic target.

Main Methods:

  • Identification and cloning of Brugia malayi IL-5 receptor binding protein (BmIL5Rbp).
  • Expression and purification of recombinant BmIL5Rbp.
  • Generation of BmIL5Rbp-specific antibodies.
  • Immunohistochemistry and immunoelectron microscopy for localization.
  • RNA interference (RNAi) to inhibit BmIL5Rbp expression.

Main Results:

  • BmIL5Rbp was identified and shown to competitively inhibit human IL-5 binding to its receptor.
  • The molecule localizes to the cuticle of B. malayi and is released in excretory/secretory products.
  • RNAi successfully reduced BmIL5Rbp mRNA and protein levels, surface expression, and release in secretions.
  • BmIL5Rbp acts as a parasite-encoded IL-5 receptor antagonist.

Conclusions:

  • BmIL5Rbp is a parasite-derived inhibitor of human IL-5 signaling.
  • This molecule may locally suppress host eosinophil activation, aiding parasite survival.
  • BmIL5Rbp represents a potential target for developing novel anti-filarial therapies.
Keywords:
Brugia malayiRNAihost-parasite defenseinterleukin-5

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