CD38 modulates respiratory syncytial virus‐driven proinflammatory processes in human monocyte‐derived dendritic cells. Issue 1 (18th December 2017)

• Record Type: Journal Article
• Authors: Schiavoni, Ilaria; Scagnolari, Carolina; Horenstein, Alberto L.; Leone, Pasqualina; Pierangeli, Alessandra; Malavasi, Fabio; Ausiello, Clara M.; Fedele, Giorgio
• Is Part Of: Immunology. Volume 154:Issue 1(2018)
• Page Start: 122
• Page End: 131
• Publication Date: 2017-12-18
• Subjects: inflammation -- interferons -- monocyte‐derived dendritic cells -- respiratory syncytial virus; Immunology -- Periodicals
• DOI: 10.1111/imm.12873
• Languages: English
• ISSNs: 0019-2805

Abstract

Summary: Respiratory syncytial virus (RSV) is the most common cause of hospitalization due to bronchiolitis in infants. Although the mechanisms behind this association are not completely elucidated, they appear to involve an excessive immune response causing lung pathology. Understanding the host response to RSV infection may help in the identification of targets for therapeutic intervention. We infected in‐vitro human monocyte‐derived dendritic cells (DCs) with RSV and analysed various aspects of the cellular response. We found that RSV induces in DCs the expression of CD38, an ectoenzyme that catalyses the synthesis of cyclic ADPR (cADPR). Remarkably, CD38 was under the transcriptional control of RSV‐induced type I interferon (IFN). CD38 and a set of IFN‐stimulated genes (ISGs) were inhibited by the anti‐oxidant N‐acetyl cysteine. When CD38‐generated cADPR was restrained by 8‐Br‐cADPR or kuromanin, a flavonoid known to inhibit CD38 enzymatic activity, RSV‐induced type I/III IFNs and ISGs were markedly reduced. Taken together, these results suggest a key role of CD38 in the regulation of anti‐viral responses. Inhibition of CD38 enzymatic activity may represent an encouraging approach to reduce RSV‐induced hyperinflammation and a novel therapeutic option to treat bronchiolitis. Abstract : The infection of human dendritic cells (DC) by respiratory syncytial virus induces activation of anti‐viral and proinflammatory pathways mediated by type I IFNs and fostered by the production of reactive oxygen species (ROS). CD38, an ectoenzyme that catalyses the synthesis of cyclic ADPR (cADPR), is under the transcriptional control of RSV‐induced type I interferon (IFN). In RSV‐infected DC, CD38 activity exacerbates the activation of inflammatory and anti‐viral processes, probably through cADPR‐mediated activation of ROS; inhibition of CD38 enzymatic activity may represent a novel approach to reduce RSV‐induced hyperinflammation and airway pathology.