title: RSV infection modulates IL-15 production and MICA levels in respiratory epithelial cells.
abstract: The cytokine interleukin (IL)-15, major histocompatibility complex (MHC) class I molecules and MHC class I chain-related proteins (MIC) A and B are involved in cellular immune responses to virus infections but their role in respiratory syncytial virus (RSV) infection has not been studied. We aimed to determine how RSV infection modulates IL-15 production, MHC class I and MICA expression in respiratory epithelial cells, the molecular pathways implicated in virus-induced IL-15 production and how interferon (IFN)-γ alters RSV-induced IL-15 production and MHC class I and MICA expression. We infected respiratory epithelial cell lines (A549 and BEAS-2B cells) and primary bronchial epithelial cells with RSV and measured production of IL-15, expression of MHC I and MICA and the role of the transcription factor nuclear factor (NF)-κB. We report here that RSV increases IL-15 in respiratory epithelial cells via virus replication and NF-κB-dependent mechanisms. Furthermore, RSV infection of epithelial cells upregulated cell surface expression of MICA and levels of soluble MICA. IFN-γ upregulated RSV induction of soluble IL-15 but inhibited induction of MICA. Upregulation of IL-15, MHC I and MICA are likely to be important mechanisms in activating immune responses to RSV by epithelial cells.
authors.affiliation: Dept of Respiratory Medicine, National Heart and Lung Institute, MRC and Asthma UK Centre in Allergic Mechanisms of Asthma and Centre for Respiratory Infection, Imperial College London, London, UK.
authors.forename: M T
authors.initials: MT
authors.lastname: Zdrenghea
authors.forename: A G
authors.initials: AG
authors.lastname: Telcian
authors.forename: V
authors.initials: V
authors.lastname: Laza-Stanca
authors.forename: C M
authors.initials: CM
authors.lastname: Bellettato
authors.forename: M R
authors.initials: MR
authors.lastname: Edwards
authors.forename: A
authors.initials: A
authors.lastname: Nikonova
authors.forename: M R
authors.initials: MR
authors.lastname: Khaitov
authors.forename: N
authors.initials: N
authors.lastname: Azimi
authors.forename: V
authors.initials: V
authors.lastname: Groh
authors.forename: P
authors.initials: P
authors.lastname: Mallia
authors.forename: S L
authors.initials: SL
authors.lastname: Johnston
authors.forename: L A
authors.initials: LA
authors.lastname: Stanciu
mesh_terms: D002478:Cells, Cultured; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis* / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology; D019409:Interleukin-15 / Q000096:biosynthesis* / Q000276:immunology; D016328:NF-kappa B / Q000378:metabolism; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology*; D015854:Up-Regulation
chemical_list: D015395:Histocompatibility Antigens Class I; C569274:IL15 protein, human; D019409:Interleukin-15; C099187:MHC class I-related chain A; D016328:NF-kappa B; D007371:Interferon-gamma