Secreted filarial nematode galectins modulate host immune cells

Area of Science:

• Parasitology
• Immunology
• Molecular Biology

Background:

• Lymphatic filariasis (LF) is a debilitating mosquito-borne disease caused by filarial nematodes like Brugia malayi.
• Current LF control relies on mass drug administration with drugs ineffective against adult parasites, necessitating better understanding of host-parasite interactions.
• Filarial nematodes manipulate host immunity, characterized by a modified type 2 response during chronic infection, crucial for parasite survival.

Purpose of the Study:

• To investigate the function of Brugia malayi galectins (Bma-galectins) identified in parasite extracellular vesicles (EVs).
• To determine if Bma-galectins contribute to the immunomodulatory mechanisms underlying chronic LF.

Main Methods:

• Sequence analysis of Bma-galectins to determine homology with known galectins.
• Functional characterization of Bma-galectins using immunological assays.
• Assessing the impact of Bma-LEC-2 on macrophage polarization and T-helper 1 (Th1) cell apoptosis.

Main Results:

• Bma-galectins share high homology with mammalian galectin-9 and exhibit similar substrate affinities.
• Bma-LEC-2 was confirmed as a bioactive protein.
• Bma-LEC-2 induces alternative activation of macrophages and selective apoptosis in Th1 cells.

Conclusions:

• A secreted Brugia malayi galectin, Bma-LEC-2, possesses immunomodulatory functions.
• Bma-LEC-2 contributes to the modified type 2 immune response observed in chronic lymphatic filariasis.
• These findings offer insights into host-parasite interactions crucial for LF pathogenesis and control.