Maternal Anti-Dengue IgG Fucosylation Predicts Susceptibility to Dengue Disease in Infants
AuthorsThulin, Natalie K.
Brewer, R. Camille
Edwards, Karlie G.
Ramadoss, Nitya S.
Taubenberger, Jeffery K.
Gentles, Andrew J.
Libraty, Daniel H.
Wang, Taia T.
UMass Chan AffiliationsDepartment of Medicine, Division of Infectious Diseases and Immunology
Amino Acids, Peptides, and Proteins
Immunology of Infectious Disease
Maternal and Child Health
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AbstractInfant 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 FcgammaRIIIa signaling during infection, in turn enhancing dengue virus replication in FcgammaRIIIa(+) 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 FcgammaRIIIa enhance dengue infections.
Thulin NK, Brewer RC, Sherwood R, Bournazos S, Edwards KG, Ramadoss NS, Taubenberger JK, Memoli M, Gentles AJ, Jagannathan P, Zhang S, Libraty DH, Wang TT. 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. PMID: 32402275. Link to article on publisher's site