Changes in the number of alveolar macrophages were correlated with organism burden during Pneumocystis carinii infection. The lungs of healthy, dexamethasone-treated, and dexamethasone-treated and P. cariniiinfected rats were lavaged with phosphate-buffered saline. Counting of alveolar macrophages in the lavage fluids revealed that P. carinii infection caused a 58% decrease in the number of alveolar macrophages and that higher P. carinii organism burdens caused a more rapid decrease in alveolar macrophage number. As a control, healthy rats were challenged with the same number of organisms as that normally used to generate P. carinii infections in dexamethasone-treated rats. Thirteen days after challenge, these rats had a profound (54%) increase in alveolar macrophage number in response to the challenge, while the number of alveolar macrophages in immunosuppressed and P. carinii-infected rats had decreased significantly by this time point. These experiments created the first animal model to mimic human pneumocystis pneumonia in alveolar macrophage number alterations. Reduction of P. carinii organism numbers by treatment of rats with trimethoprim and sulfamethoxazole brought a slow rebound in alveolar macrophage number, while recovery from P. carinii infection by cessation of immunosuppression brought a rapid rebound in alveolar macrophage number. These results suggest that both the immune state of the host and P. carinii burden affect alveolar macrophage number.Immunosuppressed populations are at risk for developing a pneumonia caused by the opportunistic organism Pneumocystis carinii (renamed recently as Pneumocystis jiroveci for those strains that infect humans) (31). P. carinii now refers to those organisms that infect rats (31). Infection with pneumocystis organisms brings many changes in the lung environment, including decrease of phosphatidylcholine (27,29) and increase of sphingomyelin (T. H. Su, V. Natarajan, and W. J. Martin II, abstract from the 1992 Int. Conf. Am. Lung Assoc./Am. Thoracic Soc., Am. Rev. Resp. Dis. 145:A246, 1992), surfactant proteins A and D (22, 26) and the adhesion proteins vitronectin and fibronectin (19). Pneumocystis infection also causes increases in the production of the cytokines tumor necrosis factor alpha (11, 24, 37), interleukin-8 (IL-8), 39), and gamma interferon (39); the growth factor granulocytemacrophage colony-stimulating factor (24); and the chemokine monocyte chemotactic protein 1 (2) but down-regulates the expression of the host transcription factor GATA-2 (33). An inflammatory response (41, 43) that changes alveolar macrophage and polymorphonuclear cell populations (7,42,44) is also observed during pneumocystis infection.In immunocompetent humans and animals, alveolar macrophages protect against pneumocystis infection by actively removing the organism from the alveolus. In contrast, it has been shown that alveolar macrophages from pneumocystis-infected animals do not phagocytose pneumocystis organisms to any significant degree (3,13). In addition to the defect in ...