Progression of Th2 Cell-Type Inflammation and Airway Remodeling in a Rodent Model of Naturally-Acquired Subclinical Primary Pneumocystis Infection.

Subclinical primary Pneumocystis infection is the most common pulmonary infection in early infancy, making it important to determine whether it damages the lung. Pneumocystis peaks at two to five months of age, when respiratory morbidity coincidently increases. We have documented that Pneumocystis increases mucus production in infant lungs, and animal models reveal lung lesions that warrant characterization. Here, immunocompetent rats infected at birth with Pneumocystis by co-habitation, to resemble community-acquired infection, underwent lung assessments at 45, 60, and 75 days of age. Lungs fixed by vascular perfusion to prevent collapse during necropsy were used for morphometry evaluations of mucus production, airway epithelial thickening, perivascular and peribronchiolar inflammation, and structural airway remodeling. Changes in these histological features indicate lung disease. Selected immune markers were assessed in parallel using fresh-frozen lung tissue from sibling rats of the same cages. Sequential activation of nuclear factor-κB and an increased Gata3/T-bet mRNA levels ratio, consistent with a Th2-type inflammatory response, and subacute fibrosis were recognized. Therefore, documenting subclinical Pneumocystis infection induces lung disease in the immunocompetent host. Taken together with the peak age of primary Pneumocystis infection, results warrant investigating the clinical impact of this often-subclinical infection on the severity of respiratory diseases in early infancy. This model can also be used to assess the effects of airway insults, including co-infections by recognized respiratory pathogens.