MassIVE MSV000080867

Imported Reanalysis Dataset Public PXD005814

Systematic Analysis of Cell-Type Differences in the Epithelial Secretome Reveals Insights Into Pathogenesis Of RSV-Induced Lower Respiratory Tract Infections

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Description

Lower respiratory tract infections (LRTI) from human Respiratory Syncytial Virus (RSV) are a significant cause of morbidity in children. A component of LRTI pathogenesis is due to signals generated by infected lower airway cells that alter lymphocyte populations and trigger airway remodeling. To obtain insights into this process, we applied an unbiased quantitative proteomics analysis of the RSV-induced epithelial secretory response in cells representative of the trachea (hBECs) vs small airway bronchiolar cells (hSAECs). A workflow was standardized initially using telomerase immortalized human epithelial cells that showed high reproducibility and cell-type differences in proteomic signatures of both secreted proteins and isolated nanoparticles (exosomes). Over half of secretome proteins were contained within exosomal, with the remainder originating from lysosomal and vaculolar compartments. We applied this workflow to three independently derived primary human cultures. 577 differentially expressed proteins from control supernatants and 966 differentially expressed proteins from RSV-infected cell supernatants were identified at a 1% false discovery rate (FDR). 15 proteins were unique to RSV-infected hBECs regulated by epithelial-specific ets homology factor (EHF). 106 proteins were unique to RSV-infected hSAECs enriched in proteins regulated by the NF?B transcription factor. In this latter group, we independently validated the differential expression of Chemokine (C-C Motif) Ligand 20 (CCL20)/macrophage inducible protein (MIP)3?, Thymic Stromal Lymphopoietin (TSLP) and chemokine (CC) ligand 3-like 1(CCL3-L1). CCL20/MIP3? is the most active mucin inducing factor in the RSV infected hSAEC secretome, and is differentially expressed in smaller airways in a mouse model of RSV infection. These studies provide insight into role of exosomal production in innate responses and regional differences in epithelial secretomes that participate in pathogenesis of RSV LRTI-induced airway remodeling. [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: Secretome ; RSV ; Lower respiratory tract

Contact

Principal Investigators:
(in alphabetical order) 		Yingxin Zhao, Ph.D., University of Texas Medical Branch, N/A
Submitting User: ccms

Publications

Zhao Y, Jamaluddin M, Zhang Y, Sun H, Ivanciuc T, Garofalo RP, Brasier AR.
Systematic Analysis of Cell-Type Differences in the Epithelial Secretome Reveals Insights into the Pathogenesis of Respiratory Syncytial Virus-Induced Lower Respiratory Tract Infections.
J. Immunol. Epub 2017 Mar 3.

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