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CD 38 modulates respiratory syncytial virus‐driven proinflammatory processes in human monocyte‐derived dendritic cells
Author(s) -
Schiavoni Ilaria,
Scagnolari Carolina,
Horenstein Alberto L.,
Leone Pasqualina,
Pierangeli Alessandra,
Malavasi Fabio,
Ausiello Clara M.,
Fedele Giorgio
Publication year - 2018
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12873
Subject(s) - cd38 , proinflammatory cytokine , immune system , interferon , biology , virus , immunology , bronchiolitis , monocyte , in vitro , inflammation , microbiology and biotechnology , biochemistry , stem cell , cd34
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 ( DC s) with RSV and analysed various aspects of the cellular response. We found that RSV induces in DC s the expression of CD 38, an ectoenzyme that catalyses the synthesis of cyclic ADPR ( cADPR ). Remarkably, CD 38 was under the transcriptional control of RSV ‐induced type I interferon ( IFN ). CD 38 and a set of IFN‐ stimulated genes ( ISG s) were inhibited by the anti‐oxidant N‐acetyl cysteine. When CD 38‐generated cADPR was restrained by 8‐Br‐ cADPR or kuromanin, a flavonoid known to inhibit CD 38 enzymatic activity, RSV ‐induced type I/ III IFN s and ISG s were markedly reduced. Taken together, these results suggest a key role of CD 38 in the regulation of anti‐viral responses. Inhibition of CD 38 enzymatic activity may represent an encouraging approach to reduce RSV ‐induced hyperinflammation and a novel therapeutic option to treat bronchiolitis.