Endogenous IFN- facilitates Pneumocystis infection and downregulates carbohydrate receptors in CD4⁺ T cell-depleted mice

IFN-gamma plays a critical role in host defense against intracellular pathogens. IFN-gamma is produced in the bronchoalveolar lavage fluid of mice infected with Pneumocystis, but the role of IFN-gamma in host defense against Pneumocystis remains controversial. It has been previously reported that although exogenous IFN-gamma has beneficial effects on eradication of Pneumocystis, endogenous IFN-gamma has a negative impact on innate immunity in immunocompromised hosts. Surprisingly, CD4(+) T cell-depleted IFN-gamma deficient (GKO) mice exhibit resistance to Pneumocystis. Alveolar macrophages (AM) from GKO mice exhibit higher expression of macrophage mannose receptor (MMR) and Dectin-1. Concomitantly, they exhibited greater ability to phagocytize Pneumocystis, and this activity was suppressed by inhibitors of these receptors. Incubation with IFN-gamma resulted in a reduction in both the expression of these receptors on AM and their Pneumocystis-phagocytic activity. These results indicate that endogenous IFN-gamma facilitates Pneumocystis to escape from host innate immunity by attenuating the phagocytic activity of AM via downregulation of MMR and Dectin-1.