Mono-(2-ethylhexyl) phthalate Promotes Dengue Virus Infection by Decreasing IL-23-Mediated Antiviral Responses.
Front Immunol. 2021 ;12:599345. Epub 2021 Feb 15. PMID: 33659001
Exposure to environmental hormones such as di(2-ethylhexyl) phthalate (DEHP) has become a critical human health issue globally. This study aimed to investigate the correlations between DEHP/mono-(2-ethylhexyl) phthalate (MEHP) levels and macrophage-associated immune responses and clinical manifestations in dengue virus (DV)-infected patients. Among 89 DV-infected patients, those with DV infection-related gastrointestinal (GI) bleeding (n = 13, 15% of patients) had significantly higher DEHP exposure than those without GI bleeding (n = 76, 85% of patients), which were 114.2 ng/ml versus 52.5 ng/mlΣDEHP in urine; p = 0.023). In anstudy using cultured human monocyte-derived macrophages (MDMs) to investigate the effects of MEHP, treatment increased IL-1β and TNF-α release but decreased IL-23 release, with negative correlations observed between urine ΣDEHP and serum IL-23 levels in patients. MEHP-treated MDMs had lower antiviral Th17 response induction activity in mixed T-cell response tests. Thedata showed that MEHP increased DV viral load and decreased IL-23 release dose-dependently, and adding IL-23 to MEHP-exposed MDMs significantly reduced the DV viral load. MEHP also suppressed IL-23 expressionthe peroxisome proliferator-activated receptor-gamma (PPAR-γ) pathway. Further, the PPAR-γ antagonist GW9662 significantly reversed MEHP-induced IL-23 suppression and reduced the DV viral load. These study findings help to explain the associations between high MEHP levels and the high global burden of dengue disease.