TY - JOUR
T1 - Brugia malayi galectin 2 is a tandem-repeat type galectin capable of binding mammalian polysaccharides
AU - Hertz, Marla I.
AU - Glaessner, Philip M.
AU - Rush, Amy
AU - Budge, Philip J.
N1 - Funding Information:
This work was supported by the National Institute for Allergy and Infectious Disease (NIAID) [grant number K08AI121422 (PJB)] and an NIH Loan Repayment Programs (NIAID) award (PJB). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.
Funding Information:
This work was supported by the National Institute for Allergy and Infectious Disease (NIAID) [grant number K08AI121422 (PJB)] and an NIH Loan Repayment Programs (NIAID) award (PJB). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.
Publisher Copyright:
© 2019 The Authors
PY - 2020/1
Y1 - 2020/1
N2 - Galectins are among the most abundant excretory/secretory (ES) products of filarial worms, but their role in filarial biology is poorly understood. Galectin-2 (Lec-2), a major component of Brugia malayi extracellular vesicles, is released by filarial worms, and was recently identified in the serum of persons with loiasis. We therefore sought to clone and characterize Lec-2, and to develop reagents to examine its potential as a biomarker and its role in parasite biology. We cloned and expressed recombinant B. malayi Lec-2 (rBmLec-2), generated a Lec-2-specific monoclonal antibody (4B4), and used it to confirm the presence of Lec-2 in B. malayi ES products and whole worm lysate. We show that Lec-2 is absent in B. malayi oocytes, and increases in concentration as embryos mature. Recombinant BmLec-2 hemagglutinates rabbit red blood cells at concentrations less than 1 μg/mL, and this is abrogated by single amino acid substitutions in the predicted carbohydrate recognition domains. rBmLec-2 binds multiple LacNAc oligosaccharides on a mammalian carbohydrate array. Sera from 17/23 (78 %) persons with microfilaremic loiasis and 4/10 (40 %) persons with bancroftian filariasis had detectable antibody to Lec-2 by western blot. Our studies confirm the functionality of BmLec-2 and indicate anti-Lec-2 antibody responses are common in persons with filariasis. These studies set the stage for further examination of the role of Lec-2 in filarial biology and in filarial-host interactions.
AB - Galectins are among the most abundant excretory/secretory (ES) products of filarial worms, but their role in filarial biology is poorly understood. Galectin-2 (Lec-2), a major component of Brugia malayi extracellular vesicles, is released by filarial worms, and was recently identified in the serum of persons with loiasis. We therefore sought to clone and characterize Lec-2, and to develop reagents to examine its potential as a biomarker and its role in parasite biology. We cloned and expressed recombinant B. malayi Lec-2 (rBmLec-2), generated a Lec-2-specific monoclonal antibody (4B4), and used it to confirm the presence of Lec-2 in B. malayi ES products and whole worm lysate. We show that Lec-2 is absent in B. malayi oocytes, and increases in concentration as embryos mature. Recombinant BmLec-2 hemagglutinates rabbit red blood cells at concentrations less than 1 μg/mL, and this is abrogated by single amino acid substitutions in the predicted carbohydrate recognition domains. rBmLec-2 binds multiple LacNAc oligosaccharides on a mammalian carbohydrate array. Sera from 17/23 (78 %) persons with microfilaremic loiasis and 4/10 (40 %) persons with bancroftian filariasis had detectable antibody to Lec-2 by western blot. Our studies confirm the functionality of BmLec-2 and indicate anti-Lec-2 antibody responses are common in persons with filariasis. These studies set the stage for further examination of the role of Lec-2 in filarial biology and in filarial-host interactions.
KW - Filariasis
KW - Galectin
KW - Lectin
KW - Loiasis
KW - Lymphatic filariasis
UR - https://www.scopus.com/pages/publications/85077620957
U2 - 10.1016/j.molbiopara.2019.111233
DO - 10.1016/j.molbiopara.2019.111233
M3 - Article
C2 - 31738955
AN - SCOPUS:85077620957
SN - 0166-6851
VL - 235
JO - Molecular and Biochemical Parasitology
JF - Molecular and Biochemical Parasitology
M1 - 111233
ER -