RSV infection modulates IL-15 production and MICA levels in respiratory epithelial cells

Zdrenghea, Dumitru; Telcian, Aurica G.; Laza-Stanca, Vasile; Bellettato, Cinzia Maria; Edwards, Michael R.; Nikonova, Alexandra; Khaitov, Musa; Azimi, Nazli; Groh, Veronika; Mallia, Patrick; Johnston, Sebastian L.; Stanciu, Luminita A.

doi:10.1183/09031936.00099811

Cited by 42 publications

(44 citation statements)

References 33 publications

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“…It is known that the ciliated epithelium secretes a number of anti-viral and anti-microbial agents, including defensins and antimicrobial peptides. In our study, the level of the anti-viral cytokine interferon-c was three-fold higher in the ciliated cell system compared with the basal cell system, and this may reduce viral yield through the activation of host transcription factors [22]. However, there are limitations in directly comparing these two culture systems.…”

Section: Basal Cell Cultures Infected With Rsv Increase Secretion Of mentioning

confidence: 84%

Ciliary dyskinesia is an early feature of respiratory syncytial virus infection

et al. 2013

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Respiratory syncytial virus is a major cause of respiratory disease. There are conflicting accounts of the response of human epithelial cells to respiratory syncytial virus and a lack of data on its effect on ciliary function. Our aim was to study the early stages of respiratory syncytial virus infection of primary human basal and ciliated cultures.Using high speed videomicroscopy, we found that ciliary beat frequency was unaffected by respiratory syncytial virus infection over 72 h; however, ciliary dyskinesia significantly increased within 24 h of infection (p,0.05). Transmission electron microscopy revealed that ultrastructural abnormalities were confined to ciliated cells, including increased cilia loss and mitochondrial damage. Confocal immunofluorescence microscopy showed that respiratory syncytial virus antigen gradually spread from the cell surface to the ciliary tip of infected cells over 3 days. Interestingly, ciliated cultures secreted fewer viruses than basal (progenitor) cell cultures and produced a chemokine response focused on recruitment of neutrophils.This study highlights differences in infection models and underscores the need to explore further the role of ciliated cells in the establishment of respiratory syncytial virus infection.Increased ciliary dyskinesia combined with ciliary loss and epithelial damage is likely to result in reduced mucociliary clearance early in the infective process. @ERSpublications Increased ciliary dyskinesia with ciliary loss and epithelial damage can result in reduced mucociliary clearance

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Section: Basal Cell Cultures Infected With Rsv Increase Secretion Of mentioning

confidence: 84%

Ciliary dyskinesia is an early feature of respiratory syncytial virus infection

et al. 2013

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“…Furthermore, the expression of IL-15 is induced in DCs upon LPS or IFN-γ stimulation and is elevated in epithelial cells by infection (7,8). Transcription factors such as NF-κB and IFN regulatory factor 1 (IRF-1) reportedly function in its expression (9)(10)(11).…”

mentioning

confidence: 99%

Characterization of the IL-15 niche in primary and secondary lymphoid organs in vivo

Cui

Hara

Simmons

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

151

137

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Significance IL-15 is a cytokine critical for development and maintenance of T lymphoid cells. However, the identity and distribution of IL-15–expressing cells in lymphoid organs are not well understood. The present study reveals, by using IL-15–CFP knock-in mice that IL-15 was expressed in subsets of thymic epithelial cells, bone marrow stromal cells, lymph node stromal cells, and blood endothelial cells, a unique perspective of IL-15 niche in immune microenvironment. Taken together with our previous observation on IL-7–producing cells, this study suggests that some stromal cells express IL-7 and IL-15 differentially. Thus, the immune microenvironment appears to be consisted of functionally distinct subsets of stromal cells, expressing different cytokines.

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“…It has been revealed that deficits of IL-15 in asthmatic patients result from an impaired response to Rhinovirus infection in vitro, which possible indicates that the cytokine has a protective effect against such infections (22). The respiratory syncytial virus was found to contribute to the upregulation of IL-15 in a study on bronchial and alveolar epithelial cell lines (43). Moreover, there is evidence that IL-15 is a significant factor responsible for the production of CD8 + memory T cells in response to viral infection (44).…”

Section: Discussionmentioning

confidence: 98%

Role of IL‑15 in the modulation of TGF‑β1‑mediated inflammation in asthma

et al. 2017

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Abstract. Transforming growth factor (TGF)-β1 has an essential role in bronchitis and the induction of bronchial remodelling, which are critical processes in the pathogenesis of asthma. However, the role of interleukin (IL)-15 in asthma inflammation remains unclear. The aim of the present study was to evaluate the effect of TGF-β1 mRNA expression on IL-15 mRNA expression in asthmatic patients and to assess the role of IL-15 in the clinical course of asthma. The study included 221 participants, comprising 130 patients with asthma and 91 healthy volunteers. The participants were subjected to testing using spirometry, as well as the Asthma Control Test™ and Borg Scale. The expression of TGF-β1 and IL-15 mRNA was analyzed in blood samples using reverse transcription-quantitative polymerase chain reaction. Statistical analysis indicated that IL-15 and TGF-β1 mRNA expression each differed significantly between the patient and control groups (P= 0.0016 and P= 0.033, respectively). A significant correlation was identified between IL-15 expression and TGF-β1 expression (R=0.41, P=0.0005). No correlation was observed between IL-15 expression and the degree of asthma severity, the results of spirometric examination or the frequency of asthma exacerbations. Further analysis revealed that IL-15 expression was elevated following the administration of inhaled glucocorticosteroids (iGCs; P=0.024), and reduced following methylxanthine treatment (P<0.001). The occurrence of dyspnoea differed between the study and control groups, and this was not found to be associated with IL-15 expression. Since IL-15 expression was correlated with TGF-β1 expression among asthmatic patients, and IL-15 expression was elevated following iGC administration, the results of the study suggest that IL-15 activity might be associated with the pathogenesis of asthma.

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RSV infection modulates IL-15 production and MICA levels in respiratory epithelial cells

Cited by 42 publications

References 33 publications

Ciliary dyskinesia is an early feature of respiratory syncytial virus infection

Ciliary dyskinesia is an early feature of respiratory syncytial virus infection

Characterization of the IL-15 niche in primary and secondary lymphoid organs in vivo

Role of IL‑15 in the modulation of TGF‑β1‑mediated inflammation in asthma

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