Juvenile, but Not Adult, Mice Display Increased Myeloid Recruitment and Extracellular Matrix Remodeling during Respiratory Syncytial Virus Infection
Abstract
Early life respiratory syncytial virus (RSV) infection has been linked to the onset of asthma. Despite this association, our knowledge of the progression of the initial viral infection is limited, and no safe or effective vaccine currently exists. Bronchioalveolar lavage, whole-lung cellular isolation, and gene expression analysis were performed on 3-wk- (juvenile) and 8-wk-old (adult) RSV-infected C57BL/6 mice to investigate age-related differences in immunologic responses; juvenile mice displayed a sustained myeloid infiltrate (including monocytes and neutrophils) with increased RNA expression of Ccl2, Ccl3, and Ccl4, when compared with adult mice, at 72 h postinfection. Juvenile mice demonstrated αSma expression (indicative of myofibroblast activity), increased hyaluronan deposition in the lung parenchyma (attributed to asthma progression), and a lack of CD64 upregulation on the surface of monocytes (which, in conjunction with serum amyloid P, is responsible for clearing residual hyaluronan and cellular debris). RSV infection of human airway epithelial cell, human lung fibroblast, and U937 monocyte cocultures (at air-liquid interface) displayed similar CCL expression and suggested matrix metalloproteinase-7 and MMP9 as possible extracellular matrix modifiers. These mouse data, in conjunction with our findings in human monocytes, suggest that the sustained influx of myeloid cells in the lungs of juvenile mice during acute RSV infection could potentiate extracellular matrix remodeling, facilitating conditions that support the development of asthma.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Dec 01, 2020
- Source ID
- 10.4049/jimmunol.2000683
Entities
People
- Jason S. Debley
- Kaitlyn A. Barrow
- Stephen R Reeves
- Steven F Ziegler
- Thomas N Wight
Organizations
- Benaroya Research Institute
- National Institute of Allergy and Infectious Diseases
- National Institutes of Health
- Seattle Children's
- United States Army
- University of Washington