STAT6 inhibitory peptide given during RSV infection of neonatal mice reduces exacerbated airway responses upon adult reinfection
Abstract
Respiratory syncytial virus (RSV)-related hospitalization during infancy is strongly associated with the subsequent development of asthma. Early life RSV infection results in a Th2-biased immune response, which is also typical of asthma. Murine models of neonatal RSV infection have been developed to examine the possible contribution of RSV-driven Th2 responses to the development of airway hyper-responsiveness later in childhood. We have investigated the ability of a cell-penetrating STAT6 inhibitory peptide (STAT6-IP), when delivered selectively during neonatal RSV infection, to modify pathogenesis induced upon secondary RSV reinfection of adults 6 wk later. Neonatal STAT6-IP treatment inhibited the development of airway hyper-responsiveness (AHR) and significantly reduced lung eosinophilia and collagen deposition in adult mice following RSV reinfection. STAT6-IP-treated, RSV-infected neonates had reduced levels of both IL-4 and alternatively activated macrophages (AAMs) in the lungs. Our findings suggest that targeting STAT6 activity at the time of early-life RSV infection may effectively reduce the risk of subsequent asthma development.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Aug 26, 2016
- Source ID
- 10.1189/jlb.4a0215-062rr
Entities
People
- Bharat T. Srinivasa
- Brian J. Ward
- Elizabeth D Fixman
- Jichuan Shan
- Katherine H. Restori
- Louis Cyr
- Soojin Lee
- Xing Li
Organizations
- Canadian Institutes of Health Research
- McGill University
- McGill University Health Centre
- Natural Sciences and Engineering Research Council
- United States Department of Defense