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

• Published in: Frontiers in immunology Vol. 11; p. 596841
• Main Authors: Dickinson, Matthew, Kliszczak, Anna E, Giannoulatou, Eleni, Peppa, Dimitra, Pellegrino, Pierre, Williams, Ian, Drakesmith, Hal, Borrow, Persephone
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 24.11.2020
• Subjects: activin; Biomarkers; cytokine; Cytokines - blood; Cytokines - metabolism; dendritic cell; Dendritic Cells - immunology; Dendritic Cells - metabolism; HIV; HIV Infections - immunology; HIV Infections - metabolism; HIV Infections - virology; HIV-1 - immunology; Host-Pathogen Interactions - immunology; Humans; Immunity, Innate; Immunology; interferon; TGF-beta; Transforming Growth Factor beta - blood; Transforming Growth Factor beta - metabolism; cytokine; TGF-beta; HIV; activin; interferon; bone morphogenetic protein; dendritic cell; innate response
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2020.596841

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)-β 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-β 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-β superfamily cytokines from plasmacytoid dendritic cells (DCs) , putatively explaining their differing 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-β superfamily cytokines, to enable appropriate modulation for therapeutic purposes.