Monomeric IgA Antagonizes IgG-Mediated Enhancement of DENV Infection

Dengue virus (DENV) is a prevalent human pathogen, infecting approximately 400 million individuals per year and causing symptomatic disease in approximately 100 million. A distinct feature of dengue is the increased risk for severe disease in some individuals with preexisting DENV-specific immunity....

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Adam D. Wegman, Hengsheng Fang, Alan L. Rothman, Stephen J. Thomas, Timothy P. Endy, Michael K. McCracken, Jeffrey R. Currier, Heather Friberg, Gregory D. Gromowski, Adam T. Waickman
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	Dengue DENV antibody dependent enhancement IgA ADE Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/4682c9b4478a45098e43e2013851ecef
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:4682c9b4478a45098e43e2013851ecef
record_format	dspace
spelling	oai:doaj.org-article:4682c9b4478a45098e43e2013851ecef2021-11-30T19:16:26ZMonomeric IgA Antagonizes IgG-Mediated Enhancement of DENV Infection1664-322410.3389/fimmu.2021.777672https://doaj.org/article/4682c9b4478a45098e43e2013851ecef2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.777672/fullhttps://doaj.org/toc/1664-3224Dengue virus (DENV) is a prevalent human pathogen, infecting approximately 400 million individuals per year and causing symptomatic disease in approximately 100 million. A distinct feature of dengue is the increased risk for severe disease in some individuals with preexisting DENV-specific immunity. One proposed mechanism for this phenomenon is antibody-dependent enhancement (ADE), in which poorly-neutralizing IgG antibodies from a prior infection opsonize DENV to increase infection of Fc gamma receptor-bearing cells. While IgM and IgG are the most commonly studied DENV-reactive antibody isotypes, our group and others have described the induction of DENV-specific serum IgA responses during dengue. We hypothesized that monomeric IgA would be able to neutralize DENV without the possibility of ADE. To test this, we synthesized IgG and IgA versions of two different DENV-reactive monoclonal antibodies. We demonstrate that isotype-switching does not affect the antigen binding and neutralization properties of the two mAbs. We show that DENV-reactive IgG, but not IgA, mediates ADE in Fc gamma receptor-positive K562 cells. Furthermore, we show that IgA potently antagonizes the ADE activity of IgG. These results suggest that levels of DENV-reactive IgA induced by DENV infection might regulate the overall IgG mediated ADE activity of DENV-immune plasma in vivo, and may serve as a predictor of disease risk.Adam D. WegmanHengsheng FangAlan L. RothmanStephen J. ThomasStephen J. ThomasTimothy P. EndyMichael K. McCrackenJeffrey R. CurrierHeather FribergGregory D. GromowskiAdam T. WaickmanAdam T. WaickmanFrontiers Media S.A.articleDengueDENVantibody dependent enhancementIgAADEImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Dengue DENV antibody dependent enhancement IgA ADE Immunologic diseases. Allergy RC581-607
spellingShingle	Dengue DENV antibody dependent enhancement IgA ADE Immunologic diseases. Allergy RC581-607 Adam D. Wegman Hengsheng Fang Alan L. Rothman Stephen J. Thomas Stephen J. Thomas Timothy P. Endy Michael K. McCracken Jeffrey R. Currier Heather Friberg Gregory D. Gromowski Adam T. Waickman Adam T. Waickman Monomeric IgA Antagonizes IgG-Mediated Enhancement of DENV Infection
description	Dengue virus (DENV) is a prevalent human pathogen, infecting approximately 400 million individuals per year and causing symptomatic disease in approximately 100 million. A distinct feature of dengue is the increased risk for severe disease in some individuals with preexisting DENV-specific immunity. One proposed mechanism for this phenomenon is antibody-dependent enhancement (ADE), in which poorly-neutralizing IgG antibodies from a prior infection opsonize DENV to increase infection of Fc gamma receptor-bearing cells. While IgM and IgG are the most commonly studied DENV-reactive antibody isotypes, our group and others have described the induction of DENV-specific serum IgA responses during dengue. We hypothesized that monomeric IgA would be able to neutralize DENV without the possibility of ADE. To test this, we synthesized IgG and IgA versions of two different DENV-reactive monoclonal antibodies. We demonstrate that isotype-switching does not affect the antigen binding and neutralization properties of the two mAbs. We show that DENV-reactive IgG, but not IgA, mediates ADE in Fc gamma receptor-positive K562 cells. Furthermore, we show that IgA potently antagonizes the ADE activity of IgG. These results suggest that levels of DENV-reactive IgA induced by DENV infection might regulate the overall IgG mediated ADE activity of DENV-immune plasma in vivo, and may serve as a predictor of disease risk.
format	article
author	Adam D. Wegman Hengsheng Fang Alan L. Rothman Stephen J. Thomas Stephen J. Thomas Timothy P. Endy Michael K. McCracken Jeffrey R. Currier Heather Friberg Gregory D. Gromowski Adam T. Waickman Adam T. Waickman
author_facet	Adam D. Wegman Hengsheng Fang Alan L. Rothman Stephen J. Thomas Stephen J. Thomas Timothy P. Endy Michael K. McCracken Jeffrey R. Currier Heather Friberg Gregory D. Gromowski Adam T. Waickman Adam T. Waickman
author_sort	Adam D. Wegman
title	Monomeric IgA Antagonizes IgG-Mediated Enhancement of DENV Infection
title_short	Monomeric IgA Antagonizes IgG-Mediated Enhancement of DENV Infection
title_full	Monomeric IgA Antagonizes IgG-Mediated Enhancement of DENV Infection
title_fullStr	Monomeric IgA Antagonizes IgG-Mediated Enhancement of DENV Infection
title_full_unstemmed	Monomeric IgA Antagonizes IgG-Mediated Enhancement of DENV Infection
title_sort	monomeric iga antagonizes igg-mediated enhancement of denv infection
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/4682c9b4478a45098e43e2013851ecef
work_keys_str_mv	AT adamdwegman monomericigaantagonizesiggmediatedenhancementofdenvinfection AT hengshengfang monomericigaantagonizesiggmediatedenhancementofdenvinfection AT alanlrothman monomericigaantagonizesiggmediatedenhancementofdenvinfection AT stephenjthomas monomericigaantagonizesiggmediatedenhancementofdenvinfection AT stephenjthomas monomericigaantagonizesiggmediatedenhancementofdenvinfection AT timothypendy monomericigaantagonizesiggmediatedenhancementofdenvinfection AT michaelkmccracken monomericigaantagonizesiggmediatedenhancementofdenvinfection AT jeffreyrcurrier monomericigaantagonizesiggmediatedenhancementofdenvinfection AT heatherfriberg monomericigaantagonizesiggmediatedenhancementofdenvinfection AT gregorydgromowski monomericigaantagonizesiggmediatedenhancementofdenvinfection AT adamtwaickman monomericigaantagonizesiggmediatedenhancementofdenvinfection AT adamtwaickman monomericigaantagonizesiggmediatedenhancementofdenvinfection
_version_	1718406319781707776

Monomeric IgA Antagonizes IgG-Mediated Enhancement of DENV Infection

Ejemplares similares