Here we demonstrate through the use of IL-22BP-knockout mice (il-22ra2<sup>-/-</sup>) that a pro-IL-22 environment reduces pulmonary inflammation during H1N1 (PR8/34 H1N1) infection and protects the lung by promoting tight junction formation.
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.
Thus, the resistance of newborn mice to pneumonia relied on commensal bacteria-directed ILC3 influx into the lungs, which mediated IL-22-dependent host resistance to pneumonia during this developmental window.
Delayed clearance of the bacteria and stronger lung inflammation observed in infected CS-exposed mice were associated with an altered production of IL-17 and IL-22 by innate immune cells.
Recent data show the involvement in COPD pathophysiology of interleukin (IL)-17 and IL-22, two cytokines that are important in the control of lung inflammation and infection.
This study demonstrated that the IL-22/IL-22BP system plays a major role during Pseudomonas aeruginosa pneumonia by moderating neutrophil accumulation in the lungs that ultimately leads to epithelium protection.