Dynamics of Transforming Growth Factor (TGF)-β Superfamily Cytokine Induction During HIV-1 Infection Are Distinct From Other Innate Cytokines

Dickinson, Matthew and Kliszczak, Anna E. and Giannoulatou, Eleni and Peppa, Dimitra and Pellegrino, Pierre and Williams, Ian and Drakesmith, Hal and Borrow, Persephone (2020) Dynamics of Transforming Growth Factor (TGF)-β Superfamily Cytokine Induction During HIV-1 Infection Are Distinct From Other Innate Cytokines. Frontiers in Immunology, 11. ISSN 1664-3224

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Link to published document: http://doi.org/10.3389/fimmu.2020.596841

Abstract

Human immunodeficiency virus type 1 (HIV-1) infection triggers rapid induction of multiple innate cytokines including type I interferons, which play important roles in viral control and disease pathogenesis. The transforming growth factor (TGF)-beta superfamily is a pleiotropic innate cytokine family, some members of which (activins and bone morphogenetic proteins (BMPs)) were recently demonstrated to exert antiviral activity against Zika and hepatitis B and C viruses but are poorly studied in HIV-1 infection. Here, we show that TGF-beta1 is systemically induced with very rapid kinetics (as early as 1-4 days after viremic spread begins) in acute HIV-1 infection, likely due to release from platelets, and remains upregulated throughout infection. Contrastingly, no substantial systemic upregulation of activins A and B or BMP-2 was observed during acute infection, although plasma activin levels trended to be elevated during chronic infection. HIV-1 triggered production of type I interferons but not TGF-beta superfamily cytokines from plasmacytoid dendritic cells (DCs) in vitro, putatively explaining their differing in vivo induction; whilst lipopolysaccharide (but not HIV-1) elicited activin A production from myeloid DCs. These findings underscore the need for better definition of the protective and pathogenic capacity of TGF-beta superfamily cytokines, to enable appropriate modulation for therapeutic purposes.

Item Type: Article
Subjects: R Medicine > R Medicine (General)
Depositing User: Repository Administrator
Date Deposited: 12 Oct 2021 03:18
Last Modified: 12 Oct 2021 03:18
URI: http://eprints.victorchang.edu.au/id/eprint/1139

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