CD38 modulates respiratory syncytial virus-driven proinflammatory processes in human monocyte-derived dendritic cells

Ilaria Schiavoni, Carolina Scagnolari, Alberto L. Horenstein, Pasqualina Leone, Alessandra Pierangeli, Fabio Malavasi, Clara M. Ausiello, Giorgio Fedele

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
JournalImmunology
DOIs
Publication statusAccepted/In press - Jan 1 2017

Keywords

  • Inflammation
  • Interferons
  • Monocyte-derived dendritic cells
  • Respiratory syncytial virus

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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