Journal of immunology research
Pdcd1-/- Mice Exhibit High Susceptibility to Respiratory Syncytial Virus Infection
By Zhang C, Guan W, Zhang Y and 4 others.
Abstract
Background
Respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract illness in infants, yet no highly effective treatment exists. The widely used BALB/c mouse model is only semipermissive to RSV and does not fully recapitulate the severe disease seen in humans, highlighting the need for improved preclinical models.
Methods
WT and Pdcd1-/- mice were challenged intranasally (i.n.) with a low dose of RSV (106 PFU). Disease severity was assessed by weight loss, lung function, viral load, and histopathology. Immune responses were characterized via flow cytometry, immunohistochemistry, and cytokine/chemokine measurement.
Results
Compared to WT mice, Pdcd1-/- mice developed significantly more severe illness, evidenced by exacerbated weight loss, lung dysfunction, histopathology, and elevated viral replication. The acute phase was marked by robust neutrophil lung infiltration, elevated chemokines (CXCL1 and CXCL2), and heightened myeloperoxidase (Mpo) activity. Pdcd1 knockout skewed the adaptive immune response, promoting a Th2-biased CD4+ T cell infiltration while impairing CD8+ T cell cytotoxicity, as indicated by reduced perforin and granzyme B expression. Critically, Pdcd1-/- mice exhibited a profound defect in antiviral cytokine production, with significantly lower levels of both IFN-γ and IFN-α in lungs and serum postinfection.