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

Abstract

IFN‐γ plays a critical role in host defense against intracellular pathogens. IFN‐γ is produced in the bronchoalveolar lavage fluid of mice infected with Pneumocystis, but the role of IFN‐γ in host defense against Pneumocystis remains controversial. It has been previously reported that although exogenous IFN‐γ has beneficial effects on eradication of Pneumocystis, endogenous IFN‐γ has a negative impact on innate immunity in immunocompromised hosts. Surprisingly, CD4+ T cell‐depleted IFN‐γ 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‐γ resulted in a reduction in both the expression of these receptors on AM and their Pneumocystis‐phagocytic activity. These results indicate that endogenous IFN‐γ facilitates Pneumocystis to escape from host innate immunity by attenuating the phagocytic activity of AM via downregulation of MMR and Dectin‐1.