Our studies also show that PIV depletes IL-22 <i>in vivo</i> Moreover, PIV-mediated enhancement of pneumonia and disease severity was dependent on the expression of pneumolysin (Ply), a prominent virulence factor of <i>S. pneumoniae</i> Altogether, we reveal that PIV and Ply additively potentiate pneumonia in a murine model of lung infection.<b>IMPORTANCE</b><i>S. pneumoniae</i> remains the leading cause of bacterial pneumonia despite widespread use of pneumococcal vaccines, forcing the necessity for appropriate treatment to control pneumococcal infections.Coinfections involving <i>S. pneumoniae</i> with other bacterial pathogens threaten antibiotic treatment strategies and disease outcomes.