PNEUMOCYSTIS-CARINII PNEUMONIA IN SCID INDUCED BY VIABLE ORGANISMS PROPAGATED IN-VITRO

Pneumocystis carinii pneumonia remains a major cause of morbidity and mortality in human immunodeficiency virus-infected individuals, despit e the widespread use of prophylaxis and the development of new chemoth erapeutic agents, The study of P. carinii and of pulmonary host defens es directed against it has been limited by lack of reliable, reproduci ble methods to obtain pure populations of organisms in useful quantiti es, While recent success has been achieved with cultures of rat P. car inii organisms, cultures of mouse P. carinii organisms have not been s uccessful. Experiments were performed to determine whether P. carinii organisms derived from mice could be propagated in vitro, Mouse P. car inii organisms, obtained from the lungs of chronically infected athymi c mice, were inoculated into spinner Basks containing HEL299 feeder ce lls seated on microcarrier beads, The numbers of mouse P. carinii orga nisms increased significantly over 7 days in culture. To test the viab ility and pathogenicity of these cultured organisms, P. carinii organi sms were harvested after 7 days of culture and were inoculated intratr acheally into susceptible scid mice, Four weeks after inoculation, sci d mice developed uniformly severe P. carinii pneumonia, These studies demonstrate for the first time that mouse P. carinii organisms can be propagated in vitro. Furthermore, cultured mouse P. carinii organisms maintain their pathogenicity in an in vivo model system, This culture system will have important applications in the study of P. carinii bio logy and in the study of host defenses directed against this important opportunistic pathogen.