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.
Footnotes
Support Statement
This work was supported by grants from the Wellcome Trust (London, UK; grants 063717 and 083567/Z/07/Z for the Centre for Respiratory Infection (Imperial College London) and a Wellcome Trust travel grant 063967 to M.T. Zdrenghea); the European Respiratory Society (fellowships to M.T. Zdrenghea, A.G. Telcian, C.M. Bellettato and A. Nikonova); Asthma UK (grants 02/027 and 05/067); the British Lung Foundation (grants P04/13 and P06/3) and British Lung Foundation/Severin Wunderman Family Foundation Programme Grant 00/02; the Medical Research Council (London; MRC grant G0601236); the British Medical Association (HC Roscoe Fellowships toA.G. Telcian, V. Laza-Stanca and P. Mallia); the National Institute of Health Research Biomedical Research Centre (London) funding scheme; the European Academy of Allergy and Clinical Immunology (EAACI; Zurich, Switzerland; C.M. Bellettato, M.R. Khaitov and A. Nikonova); Imperial College London; and Union Chimique Belge (UCB) Institute ofAllergy fellowships (Brussels, Belgium).
Statement of Interest
A statement of interest for N. Azimi can be found at www.erj.ersjournals.com/site/misc/statements.xhtml
- Received June 10, 2011.
- Accepted July 28, 2011.
- ©ERS 2012