Nude rats as a model of natural Pneumocystis carinii pneumonia: sequential morphological study of lung lesions

Abstract

A spontaneous infection with Pneumocystis carinii (P.c.) caused enzootic fatal pneumonia in a long-term experiment with athymic Rowett Nude (Han:RNU rnu/rnu) and New Zealand Nude (Han:NZNU rnuN/rnuN) rats. In order to reproduce the infection and to characterize the early pathogenesis of lung lesions, 13 young athymic Han:RNU and Han:NZNU rats from P.c.-free breeding colonies were housed together in one room with chronically P.c.-infected rats. They were killed after 8, 12, 16, 20 or 24 weeks, and their lungs were examined for P.c. infection by means of light microscopy, immunohistochemistry and transmission electron microscopy. Lung lesions progressed from a mild interstitial pneumonia with scattered alveolar macrophages (8 weeks) to a severe diffuse interstitial pneumonia with widespread areas of distended alveoli, filled with foamy material. In all lungs, P.c. antigen was detected immunohistochemically, developing from small intra-alveolar aggregations of organisms into large multifocal clusters. Ultrastructurally, P.c. trophozoites and cysts were seen attached to type I pneumocytes and lying free in the alveolar lumen. Chronic severe P.c. pneumonia (20 and 24 weeks) was characterized by masses of P.c. trophozoites in the alveoli and alveolar walls, extensive proliferation of type II pneumocytes and interstitial fibrosis. The easy and consistent horizontal transmission of spontaneous P.c. pneumonia to previously non-infected athymic Han:RNU and Han:NZNU rats and the similarity of the disease to human infection demonstrate both rat strains to be excellent models for studying pulmonary pneumocystosis of immunodeficient human patients.