IFN-gamma deficiency worsen Pneumocystis pneumonia with Th17 development in nude mice

Pneumocystis pneumonia (PCP) occurs frequently in patients with immunodeficiency syndromes, especially AIDS. In order to investigate the role of IFN-gamma on PCP, nude mice deficient in IFN-gamma (GKO nude) and their wild-type ones (WT nude) were infected with murine Pneumocystis. Nine weeks later they were sacrificed, and cytokines in BALF and lung histopathology were compared between them. Cyst burden was greater in GKO than in WT nude mice. Histopathology in the lung was severer and granulomatous lesions were observed more frequently in GKO nude mice. Levels of IL-17 were higher in BALF of GKO than in that of WT nude mice. Greater number of CD4(+) T cells from lungs of infected GKO nude mice produced IL-17 than those from WT ones. These results suggest that deficiency in IFN-gamma induces the differentiation of Th17 and that IL-17 is responsible for inflammatory response in PCP.