Mono-(2-ethylhexyl) phthalate Promotes Dengue Virus Infection by Decreasing IL-23-Mediated Antiviral Responses

Abstract

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/ml ΣDEHP in urine; p = 0.023). In an in vitro study 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. The in vitro data 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 expression via the 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.

Association of Gut Microbiota With Intestinal Ischemia/Reperfusion Injury

“…In the daily diet and metabolism, the intestinal tract gathers the most important garbage and toxins in the human body, and will eventually be excreted through the feces, which is also an important channel for the excretion of more than 80% of the toxins in the human body ( Zhao et al., 2021 ; Butt and Jenab, 2021 ; Chen et al., 2021 ). In addition, more than 97.5% of the nutrients necessary for the human body are obtained from the intestinal absorption ( Tiffany et al., 2021 ); 95% of the core important hormones of the human body are produced by the intestinal tract, and it is currently known that the human gastrointestinal tract can secrete more than 35 kinds of hormones ( Mayneris-Perxachs et al., 2020 ; Lin et al., 2021 ; Qi et al., 2021 ). The intestine is the second brain of the human body, with hundreds of millions of nerve cells and a complex neural network distributed.…”

Umbilical Cord Mesenchymal Stromal/Stem Cells and Their Interplay with Th-17 Cell Response Pathway

“…IL-1β is a proinflammatory cytokine that plays a significant role in the immune response and inflammatory processes [56]. IL-1β triggers the production of other cytokines, including IL-6 and IL-23 [57]. IL-1β can suppress the inhibitory effects of IL-2 on IL-17 production through induction of IL-1R, IL-23R, and RORγt.…”

Sensitivity of Legionella pneumophila to phthalates and their substitutes

“…PAEs can also alter the molecular mechanisms leading to inflammation, on the one hand by modulating the functions and lifespan of immune cells, and on the other hand, by modifying the production patterns of cytokines 21 – 23 . These data suggest that such an endocrine disruption may have consequences for innate and adaptive immune responses 21 , 24 , and thus indirectly promote infectious diseases 25 – 27 . Furthermore, studies integrating the microbiota as a central actor are emerging since 2019.…”