Hypersensitivity pneumonitis to Paracoccidioides brasiliensis antigens in mice

Hypersensitivity pneumonitis was induced in mice immunized with Paracoccidioides brasiliensis and challenged, one week later, with soluble (SPbAg) or particulate (PPbAg) antigen (formalin-killed yeast cells), administered by the intratracheal route. Between 24 and 48 h post-challenge, animals developed an interstitial and intra-alveolar pneumonitis. Macrophages and lymphocytes arranged focally into loose or mature granulomata were observed by light and electron microscopy. The distribution and fate of antigens was studied by immunofluorescence. Three hours after challenge with SPbAg the lungs showed linear fluorescent deposits, whereas after challenge with PPbAg the pattern was globular, corresponding to the particulate antigen. After 24 and 48 h, the pattern was diffuse and finely granular in both groups, with a decreasing number of animals showing detectable fluorescence. Immunization induced a positive footpad swelling test (FPT) in all animals. After pulmonary challenge, there was a significant decrease in FPT indices, interpreted as desensitization due to trapping of specifically sensitized lymphocytes in the lungs. In conclusion, immunization induced a marked cellular immune response, the inflammatory pattern and the tempo of the induced pneumonitis being compatible with delayed hypersensitivity in the lungs. Immunized mice also cleared the injected antigens rapidly. These data suggest that hypersensitivity pneumonitis may be an expression of pulmonary resistance to infection with P. brasiliensis.