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

Area of Science:

• Immunology
• Virology
• Molecular Biology

Background:

• Respiratory syncytial virus (RSV) is a leading cause of infant hospitalization for bronchiolitis.
• The excessive immune response to RSV contributes to lung pathology, but underlying mechanisms require further elucidation.
• Identifying host response targets is crucial for developing therapeutic interventions for RSV infection.

Purpose of the Study:

• To investigate the host cellular response to RSV infection in human monocyte-derived dendritic cells (DCs).
• To explore the role of CD38 and its product cyclic ADPR (cADPR) in regulating anti-viral responses to RSV.
• To assess the therapeutic potential of inhibiting CD38 activity in RSV-induced hyperinflammation.

Main Methods:

• Infection of human monocyte-derived dendritic cells (DCs) with RSV in vitro.
• Analysis of CD38 expression and its transcriptional regulation by type I interferon (IFN).
• Assessment of the impact of CD38 inhibition (using 8-Br-cADPR and kuromanin) on RSV-induced IFN and IFN-stimulated genes (ISGs).

Main Results:

• RSV infection induced CD38 expression in DCs, regulated transcriptionally by type I IFN.
• The antioxidant N-acetyl cysteine inhibited CD38 and IFN-stimulated genes (ISGs).
• Inhibiting CD38 enzymatic activity significantly reduced RSV-induced type I/III IFNs and ISGs.

Conclusions:

• CD38 plays a critical role in regulating the host's anti-viral response to RSV.
• Inhibiting CD38 enzymatic activity shows promise for reducing RSV-induced hyperinflammation.
• Targeting CD38 may offer a novel therapeutic strategy for treating RSV-induced bronchiolitis.