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Sex-specific glycosylation of secreted immunomodulatory proteins in the filarial nematode Brugia malayi

View ORCID ProfileJoseph Koussa, Burcu Vitrinel, Peter Whitney, Brian Kasper, Lara K. Mahal, Christine Vogel, Sara lustigman, Kourosh Salehi-Ashtiani, Elodie Ghedin
doi: https://doi.org/10.1101/2021.02.24.432741
Joseph Koussa
1Department of Biology, New York University and Center for Genomics and Systems Biology (CGSB), New York, NY, USA
2Division of Science and Math, New York University Abu Dhabi, Abu Dhabi, UAE
7Systems Genomics Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
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  • ORCID record for Joseph Koussa
Burcu Vitrinel
1Department of Biology, New York University and Center for Genomics and Systems Biology (CGSB), New York, NY, USA
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Peter Whitney
1Department of Biology, New York University and Center for Genomics and Systems Biology (CGSB), New York, NY, USA
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Brian Kasper
3Department of Chemistry, New York University, New York, NY, USA
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Lara K. Mahal
3Department of Chemistry, New York University, New York, NY, USA
4Department of Chemistry, University of Alberta, Edmonton, AB, CANADA
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Christine Vogel
1Department of Biology, New York University and Center for Genomics and Systems Biology (CGSB), New York, NY, USA
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Sara lustigman
5Laboratory of Molecular Parasitology, Lindsley F. Kimball Research Institute, The New York Blood Center, New York, NY, USA
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Kourosh Salehi-Ashtiani
2Division of Science and Math, New York University Abu Dhabi, Abu Dhabi, UAE
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Elodie Ghedin
1Department of Biology, New York University and Center for Genomics and Systems Biology (CGSB), New York, NY, USA
6Department of Epidemiology, School of Global Public Health, New York University, New York, NY, USA
7Systems Genomics Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
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  • For correspondence: elodie.ghedin@nih.gov
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Abstract

The extended persistence of filarial nematodes within a host suggests immunomodulatory mechanisms that allow the parasites to resist or evade the host immune response. There is increasing evidence for immunomodulatory glycans expressed by a diversity of parasitic worms. In this study, we integrate multiple layers of the host-parasite interface to investigate the glycome of a model filarial parasite, Brugia malayi. We report a significant overrepresentation of terminal GalNAc moieties in adult female worms coupled with an overall upregulation in O-glycosylation, T-antigen expression, and a bias for galactose containing glycans. Adult males preferentially displayed a bias for terminal GlcNAc containing glycans, and fucosylated epitopes. Subsequent proteomic analysis confirmed sex-biases in protein glycosylation and highlighted the sex-specific glycosylation of well characterized immunomodulators expressed and secreted by B. malayi. We identify sex-specific effectors at that interface and suggest approaches to selectively interfere with the parasitic life cycle and potentially control transmission.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted February 24, 2021.
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Sex-specific glycosylation of secreted immunomodulatory proteins in the filarial nematode Brugia malayi
Joseph Koussa, Burcu Vitrinel, Peter Whitney, Brian Kasper, Lara K. Mahal, Christine Vogel, Sara lustigman, Kourosh Salehi-Ashtiani, Elodie Ghedin
bioRxiv 2021.02.24.432741; doi: https://doi.org/10.1101/2021.02.24.432741
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Sex-specific glycosylation of secreted immunomodulatory proteins in the filarial nematode Brugia malayi
Joseph Koussa, Burcu Vitrinel, Peter Whitney, Brian Kasper, Lara K. Mahal, Christine Vogel, Sara lustigman, Kourosh Salehi-Ashtiani, Elodie Ghedin
bioRxiv 2021.02.24.432741; doi: https://doi.org/10.1101/2021.02.24.432741

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