Maternal Anti-Dengue IgG Fucosylation Predicts Susceptibility to Dengue Disease in Infants

Natalie K Thulin; R Camille Brewer; Robert Sherwood; Stylianos Bournazos; Karlie G Edwards; Nitya S Ramadoss; Jeffery K Taubenberger; Matthew Memoli; Andrew J Gentles; Prasanna Jagannathan; Sheng Zhang; Daniel H Libraty; Taia T Wang

doi:10.1016/j.celrep.2020.107642

Maternal Anti-Dengue IgG Fucosylation Predicts Susceptibility to Dengue Disease in Infants

Cell Rep. 2020 May 12;31(6):107642. doi: 10.1016/j.celrep.2020.107642.

Affiliations

¹ Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
² Proteomics Facility, Institute of Biotechnology, Cornell University, Ithaca, NY 14853, USA.
³ The Laboratory of Molecular Genetics and Immunology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
⁴ Department of Immunology and Rheumatology, Stanford University, Stanford, CA 94305, USA.
⁵ Viral Pathogenesis and Evolution Section, Laboratory of Infectious Diseases, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
⁶ Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Biomedical Data Science, Stanford University, Stanford, CA 94305, USA.
⁷ Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA.
⁸ University of Massachusetts Medical School, Worcester, MA, USA.
⁹ Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA; Chan Zuckerberg Biohub, San Francisco, CA 94518, USA. Electronic address: taiawang@stanford.edu.

Abstract

Infant mortality from dengue disease is a devastating global health burden that could be minimized with the ability to identify susceptibility for severe disease prior to infection. Although most primary infant dengue infections are asymptomatic, maternally derived anti-dengue immunoglobulin G (IgGs) present during infection can trigger progression to severe disease through antibody-dependent enhancement mechanisms. Importantly, specific characteristics of maternal IgGs that herald progression to severe infant dengue are unknown. Here, we define ≥10% afucosylation of maternal anti-dengue IgGs as a risk factor for susceptibility of infants to symptomatic dengue infections. Mechanistic experiments show that afucosylation of anti-dengue IgGs promotes FcγRIIIa signaling during infection, in turn enhancing dengue virus replication in FcγRIIIa⁺ monocytes. These studies identify a post-translational modification of anti-dengue IgGs that correlates with risk for symptomatic infant dengue infections and define a mechanism by which afucosylated antibodies and FcγRIIIa enhance dengue infections.

Keywords: CD16; FcγRIIIa; IgG fucosylation; antibody glycosylation; infant dengue; severe dengue.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Antibodies, Anti-Idiotypic / genetics*
Dengue Virus / genetics*
Female
Humans
Infant
Infant, Newborn
Severe Dengue / virology*

Substances

Antibodies, Anti-Idiotypic
anti-IgG

Maternal Anti-Dengue IgG Fucosylation Predicts Susceptibility to Dengue Disease in Infants

Authors

Affiliations

Abstract

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MeSH terms

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