Overexpression of β-Arrestin 2 in Peripheral Blood Mononuclear Cells of Patients With Cryptococcal Meningitis

Abstract

Cryptococcal meningitis is often associated with elevated IL-10 levels, which suggest a dysregulation in the antifungal immune response. β-Arrestin 2 plays a major role in desensitization of G-protein-coupled receptors involved in the immune responses, provides a scaffolding platform for modification of many signal transduction proteins, and binds Src and MAP kinases family members. This study compared the levels of β-arrestin 2 mRNA and protein in peripheral blood mononuclear cells (PBMC) of patients with cryptococcal meningitis detected. The interferon-γ (IFN-γ) serum concentration was determined with enzyme-linked immunosorbent assay (ELISA) to reveal its relationship with β-arrestin 2. The effect of modulation of β-arrestin 2 on cytotoxic activity against Cryptococcus was explored via transfection and interference of β-arrestin 2. PBMCs of patients with cryptococcal meningitis exhibited significantly elevated levels of β-arrestin 2 and a positive correlation between β-arrestin 2 and IL-10 levels existed in patients’ serum, but a negative correlation was found between β-arrestin 2 and IFN-γ expression. In conclusion, elevated expression of β-arrestin 2 in PBMCs of patients with cryptococcal meningitis correlated with a reduced cytotoxic activity against Cryptococcus. This study suggests that reduced β-arrestin 2 mRNA levels or inhibition of β-arrestin 2 activity may augment INF-γ production, and ultimately, the anti-Cryptococcus immune response of infected patients.