Development and resolution of Pneumocystis carinii pneumonia in severe combined immunodeficient mice: a morphological study of host inflammatory responses.

The development and resolution of naturally-acquired Pneumocystis carinii pneumonia was studied in a severe combined immunodeficient (SCID) mouse model by light and electron microscopies. Initial infection was evident in 3-week-old SCID mice and started as focal alveolar colonization in the areas near terminal airways. Pronounced pulmonary inflammation occurred in animals of 10 weeks or older and the infection intensity reached a plateau in animals 12 weeks of age. At this stage of disease, the histopathological features of P. carinii infection in SCID mice were similar to those of immunodeficient man. Reconstitution of SCID mice with immunocompetent spleen cells at day 0 induced substantial pulmonary inflammation that was evident already by day 7 and most severe and extensive by day 12. The clearance of P. carinii did not begin until after day 12 and was almost completed by day 17. Alveolar macrophages in mice killed between days 12 and 15, at the time when P. carinii are being rapidly cleared, appeared active but phagocytosis of P. carinii was not commonly observed by either light or electron microscopy. These results suggest that (1) the presence of non-lymphoid inflammatory cells in SCID mice is not sufficient to control P. carinii infection; (2) the clearance of P. carinii from the lungs of reconstituted SCID mice requires local recruitment of large numbers of inflammatory cells with an active appearance; and (3) intracellular killing of P. carinii by phagocytosis does not appear to be a major mechanism in host defences against P. carinii infection in this model.