RESUMEN
Endocrine disrupting chemicals (EDCs) are chemicals that can be found in the environment and have adverse effects on human health by mimicking, perturbing and blocking the function of hormones. They are commonly studied in water surfaces, rarely in soils, although it can be an important source of their presence in the environment. Their detection in soils is analytically challenging to quantify, hence the lack of known background concentrations found in the literature. This scientific research aimed to detect EDCs in soils by analyzing 240 soil samples using an optimized protocol of double extraction and analysis using liquid chromatography coupled to mass spectrometry. The optimized protocol allowed for very sensitive detection of the targeted compounds. The results showed a high concentration of 29.391 ng/g of 17ß-estradiol in soils and 47.16 ng/g for 17α-ethinylestradiol. Testosterone and Progesterone were detected at a highest of 1.02 and 6.58 ng/g, respectively. The ∑EDCs which included estrogens, progesterone, testosterone and Bisphenol A was found at an average of 22.72 ± 35.46 ng/g in the study area. The results of this campaign showed a heterogeneous geographic distribution of the EDCs compounds in the different zones of study. Additionally, the study conducted a comparison of the concentration of EDCs in different land covers including urban areas, agricultural lands, grasslands and forests. We observed a significant difference between forests and other land covers (p < 0.0001) for 17α-ethinylestradiol, estriol, and progesterone. This presence of EDCs in forest lands is not yet understood and requires further studies concerning its origins, its fate and its effect on human health. This study is the first large-scale sampling campaign targeting EDCs in soils in Europe and the second in the world. It is also the first to assess the concentrations of these compounds based on different land covers.
Asunto(s)
Disruptores Endocrinos , Contaminantes Químicos del Agua , Humanos , Disruptores Endocrinos/análisis , Progesterona/análisis , Suelo , Contaminantes Químicos del Agua/análisis , Etinilestradiol/análisis , Testosterona , Monitoreo del AmbienteRESUMEN
Lipid droplets (LDs) are increasingly recognized as critical organelles in signalling events, transient protein sequestration and inter-organelle interactions. However, the role LDs play in antiviral innate immune pathways remains unknown. Here we demonstrate that induction of LDs occurs as early as 2 h post-viral infection, is transient and returns to basal levels by 72 h. This phenomenon occurs following viral infections, both in vitro and in vivo. Virally driven in vitro LD induction is type-I interferon (IFN) independent, and dependent on Epidermal Growth Factor Receptor (EGFR) engagement, offering an alternate mechanism of LD induction in comparison to our traditional understanding of their biogenesis. Additionally, LD induction corresponds with enhanced cellular type-I and -III IFN production in infected cells, with enhanced LD accumulation decreasing viral replication of both Herpes Simplex virus 1 (HSV-1) and Zika virus (ZIKV). Here, we demonstrate, that LDs play vital roles in facilitating the magnitude of the early antiviral immune response specifically through the enhanced modulation of IFN following viral infection, and control of viral replication. By identifying LDs as a critical signalling organelle, this data represents a paradigm shift in our understanding of the molecular mechanisms which coordinate an effective antiviral response.
Asunto(s)
Interferones/inmunología , Gotas Lipídicas/inmunología , Virosis/inmunología , Animales , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/metabolismo , Herpesvirus Humano 1/fisiología , Humanos , Inmunidad Innata , Interferones/genética , Interferones/metabolismo , Gotas Lipídicas/metabolismo , Ratones , Ácidos Nucleicos/metabolismo , Replicación Viral/efectos de los fármacos , Virus Zika/fisiologíaRESUMEN
Influenza virus gains entry into the body by inhalation and initiates its replication cycle within the lung. The early stage of infection, while the virus is confined to the lung mucosa, provides the ideal window of opportunity for an effective immune response to control the infection. Tissue-resident memory (Trm) CD8 T cells, located in a variety of tissues including the lung, are ideally situated to act during this window and stall the infection. The factors involved in the differentiation of lung Trm cells remain poorly defined. We demonstrate that recognition of antigen presented locally by dendritic cells (DCs) and transforming growth factor-ß (TGFß) signaling are both required. We exploited this knowledge to develop an antibody-targeted vaccination approach to generate lung Trm cells. Delivering antigen exclusively to respiratory DCs results in the development of lung CD8 Trm cells that are highly protective against lethal influenza challenge. Our results describe an effective vaccination strategy that protects against influenza virus infection.