DENV-specific IgA contributes protective and non-pathologic function during antibody-dependent enhancement of DENV infection Article Swipe
Adam D. Wegman
,
Mitchell J. Waldran
,
Lauren E. Bahr
,
Joseph Q. Lu
,
Kristen E. Baxter
,
Stephen J. Thomas
,
Adam T. Waickman
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1101/2023.04.01.535210
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1101/2023.04.01.535210
Dengue represents a growing public health burden worldwide, accounting for approximately 100 million symptomatic cases and tens of thousands of fatalities yearly. Prior infection with one serotype of dengue virus (DENV) is the greatest known risk factor for severe disease upon secondary infection with a heterologous serotype, a risk which increases as serotypes co-circulate in endemic regions. This disease risk is thought to be mediated by IgG-isotype antibodies raised during a primary infection, which poorly neutralize heterologous DENV serotypes and instead opsonize virions for uptake by FcγR-bearing cells. This antibody-dependent enhancement (ADE) of infection leads to a larger proportion of susceptible cells infected, higher viremia and greater immunopathology. We have previously characterized the induction of a serum IgA response, along with the typical IgM and IgG responses, during dengue infection, and have shown that DENV-reactive IgA can neutralize DENV and competitively antagonize IgG-mediated ADE. Here, we evaluate the potential for IgA itself to cause ADE. We show that IgG, but not IgA, mediated ADE of infection in cells expressing both FcαR and FcγRs. IgG-mediated ADE stimulated significantly higher pro-inflammatory cytokine production by primary human macrophages, while IgA did not affect, or slightly suppressed, this production. Mechanistically, we show that DENV/IgG immune complexes bind susceptible cells significantly more efficiently than DENV/IgA complexes or virus alone. Finally, we show that over the course of primary dengue infection, the expression of FcγRI (CD64) increases during the period of acute viremia, while FcγRIIa (CD32) and FcαR (CD89) expression decreases, thereby further limiting the ability of IgA to facilitate ADE in the presence of DENV. Overall, these data illustrate the distinct protective role of IgA during ADE of dengue infection and highlight the potential therapeutic and prognostic value of DENV-specific IgA.
Related Topics
Concepts
Dengue virus
Antibody-dependent enhancement
Dengue fever
Viremia
Antibody
Immunology
Heterologous
Biology
Immune system
Virology
Serotype
Immunoglobulin G
Isotype
Virus
Monoclonal antibody
Gene
Biochemistry
Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2023.04.01.535210
- https://www.biorxiv.org/content/biorxiv/early/2023/04/03/2023.04.01.535210.full.pdf
- OA Status
- green
- Cited By
- 3
- References
- 59
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4362512067
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4362512067Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1101/2023.04.01.535210Digital Object Identifier
- Title
-
DENV-specific IgA contributes protective and non-pathologic function during antibody-dependent enhancement of DENV infectionWork title
- Type
-
preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
-
2023Year of publication
- Publication date
-
2023-04-03Full publication date if available
- Authors
-
Adam D. Wegman, Mitchell J. Waldran, Lauren E. Bahr, Joseph Q. Lu, Kristen E. Baxter, Stephen J. Thomas, Adam T. WaickmanList of authors in order
- Landing page
-
https://doi.org/10.1101/2023.04.01.535210Publisher landing page
- PDF URL
-
https://www.biorxiv.org/content/biorxiv/early/2023/04/03/2023.04.01.535210.full.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
-
https://www.biorxiv.org/content/biorxiv/early/2023/04/03/2023.04.01.535210.full.pdfDirect OA link when available
- Concepts
-
Dengue virus, Antibody-dependent enhancement, Dengue fever, Viremia, Antibody, Immunology, Heterologous, Biology, Immune system, Virology, Serotype, Immunoglobulin G, Isotype, Virus, Monoclonal antibody, Gene, BiochemistryTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
3Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 2, 2023: 1Per-year citation counts (last 5 years)
- References (count)
-
59Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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