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

IFN- γ attenuates phagocytic activity of alveolar macrophages againstPneumocystis organisms by downregulating the expression of Dectin-1 and macrophage mannose receptor (MMR) in immunocompromised subjects. IFN- γ plays a critical role in host defense against intracellular pathogens. IFN-γ is produced in the bronchoalveolar lavage fluid of mice infected withPneumocystis, but the role of IFN- γ in host defense againstPneumocystis remains controversial. It has been previously reported that although exogenous IFN- γ has beneficial effects on eradication ofPneumocystis, 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 toPneumocystis. Alveolar macrophages (AM) from GKO mice exhibit higher expression of macrophage mannose receptor (MMR) and Dectin-1. Concomitantly, they exhibited greater ability to phagocytizePneumocystis, 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 theirPneumocystis-phagocytic activity. These results indicate that endogenous IFN- γ facilitatesPneumocystis to escape from host innate immunity by attenuating the phagocytic activity of AMvia downregulation of MMR and Dectin-1.

Source: FEBS Letters - April 18, 2024 Category: Biochemistry Authors: Yi Wang, Hisashi Nagase, Yoh ‐ichi Tagawa, Shinsuke Taki, Masaya Takamoto Tags: Research Letter Source Type: research