The compound 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), an environmental contaminant, is a potent ligand for aryl hydrocarbon receptor (AhR). In the current study, we made an exciting observation that naive C57BL/6 mice that were exposed i.p. to TCDD showed massive mobilization of myeloid-derived suppressor cells (MDSCs) in the peritoneal cavity. These MDSCs were highly immunosuppressive and attenuated Con A–induced hepatitis upon adoptive transfer. TCDD administration in naive mice also led to induction of several chemokines and cytokines in the peritoneal cavity and serum (CCL2, CCL3, CCL4, CCL11, CXCL1, CXCL2, CXCL5, CXCL9, G-CSF, GM-CSF, VEGF, and M-CSF) and chemokine receptors on MDSCs (CCR1, CCR5, and CXCR2). Treatment with CXCR2 or AhR antagonist in mice led to marked reduction in TCDD-induced MDSCs. TCDD-induced MDSCs had high mitochondrial respiration and glycolytic rate and exhibited differential microRNA (miRNA) expression profile. Specifically, there was significant downregulation of miR-150-5p and miR-543-3p. These two miRNAs targeted and enhanced anti-inflammatory and MDSC-regulatory genes, including IL-10, PIM1, ARG2, STAT3, CCL11 and its receptors CCR3 and CCR5 as well as CXCR2. The role of miRs in MDSC activation was confirmed by transfection studies. Together, the current study demonstrates that activation of AhR in naive mice triggers robust mobilization of MDSCs through induction of chemokines and their receptors and MDSC activation through regulation of miRNA expression. AhR ligands include diverse compounds from environmental toxicants, such as TCDD, that are carcinogenic to dietary indoles that are anti-inflammatory. Our studies provide new insights on how such ligands may regulate health and disease through induction of MDSCs. Key Points AhR activation leads to induction of MDSCs with immunosuppressive activity. AhR-mediated induction of MDSCs is regulated by microRNA that target CXCR2.

Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a potent ligand for AhR and a known carcinogen. While AhR activation by TCDD leads to significant immunosuppression, how this translates into carcinogenic signal is unclear. Recently, we demonstrated that activation of AhR by TCDD in naïve C57BL6 mice leads to massive induction of myeloid derived-suppressor cells (MDSCs). In the current study, we investigated the role of the gut microbiota in TCDD-mediated MDSC induction. TCDD caused significant alterations in the gut microbiome, such as increases in Prevotella and Lactobacillus, while decreasing Sutterella and Bacteroides. Fecal transplants from TCDD-treated donor mice into antibiotic-treated mice induced MDSCs and increased regulatory T-cells (Tregs). Injecting TCDD directly into antibiotic-treated mice also induced MDSCs, although to a lesser extent. These data suggested that TCDD-induced dysbiosis plays a critical role in MDSC induction. Interestingly, treatment with TCDD led to induction of MDSCs in the colon and undetectable levels of cysteine. MDSCs suppressed T cell proliferation while reconstitution with cysteine restored this response. Lastly, blocking CXC chemokine receptor 2 (CXCR2) impeded TCDD-mediated MDSC induction. Our data demonstrate that AhR activation by TCDD triggers dysbiosis which, in turn, regulates, at least in part, induction of MDSCs.

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a polyhalogenated planar hydrocarbon belonging to a group of highly toxic and persistent environmental contaminants known as “dioxins”. TCDD is an animal teratogen and carcinogen that is well characterized for causing immunosuppression through activation of aryl hydrocarbon receptor (AHR). In this study, we investigated the effect of exposure of mice to an acute dose of TCDD on the metabolic profile within the serum and cecal contents to better define the effects of TCDD on host physiology. Our findings demonstrated that within the circulating metabolome following acute TCDD exposure, there was significant dysregulation in the metabolism of bioactive lipids, amino acids, and carbohydrates when compared with the vehicle (VEH)-treated mice. These widespread changes in metabolite abundance were identified to regulate host immunity via modulating nuclear factor-kappa B (NF-κB) and extracellular signal-regulated protein kinase (ERK1/2) activity and work as biomarkers for a variety of organ injuries and dysfunctions that follow TCDD exposure. Within the cecal content of mice exposed to TCDD, we were able to detect changes in inflammatory markers that regulate NF-κB, markers of injury-related inflammation, and changes in lysine degradation, nicotinamide metabolism, and butanoate metabolism, which collectively suggested an immediate suppression of broad-scale metabolic processes in the gastrointestinal tract. Collectively, these results demonstrate that acute TCDD exposure results in immediate irregularities in the circulating and intestinal metabolome, which likely contribute to TCDD toxicity and can be used as biomarkers for the early detection of individual exposure.

Background: Weed infestation and salinity are both biotic and abiotic stresses that are highly present in the Basrah governorate in Iraq and widely influence crop growth Methods: The present work was conducted to evaluate the effect of salinity at (0, 6, 12 dS/m) and aqueous extract of Alhagi maurorum at (0, 3 g/L) on growth and biochemical parameters as well as phytocomponents of Dill plant Anethum graveolens L. Results: Results revealed that growth parameters and photopigment content increased with salinity at 12 dS/m and reduced with Alhagi maurorum aqueous extract. Besides that, carbohydrate content was reduced with both stresses, and proline content increased with Alhagi maurorum aqueous extract. GC-MS chromatogram of Anethum graveolens methanolic extract displayed high alteration in phytocomponents quantity post salinity and camelthorn extract treatments. Conclusion: Current work inferred that the Dill plant has high tolerance properties to salinity contrary to weed infestation stress. Stresses combination declined growth parameters and reduced metabolite content of Dill plants.

Previous published literatures have been established the impact of selenium application in a trace amount on yield and active constituents of basil plants. In the current study, the effect of high doses of selenium application on growth of Greek basil Ocimum basilicum var. minimum growth and its essential oil compounds was investigated. Obtained result exhibited that the foliar application with (0, 40, 80, 120, 160) mg/L of selenium reduced the plants growth parameters and plant content of phytopigments and primary metabolites such as carbohydrates, protein, and proline. Refractive index of essential oil diminished post selenium application, while, specific gravity increased at 160 mg/L. Selenium application also caused alteration in the secondary metabolites profile. A reduction was obtained in the volatile compounds of essential oil such as Linalool, Eugenol and Methyleugenol with selenium treatment. On the other hand, unsaturated fatty acids such as Linolenic acid and phytosterols such as Campesterol, Stigmasterol and beta-Sitosterol increased with applicated selenium concentration.

Tomato (Solanum lycopersicum L.) is the most popular vegetable crop in the world. It is grown almost all over the world. The biggest challenge in producing this crop is diseases caused by Fusarium oxysporum. In developing eco-friendly antifungal selective substances for controlling Fusarium diseases, the role of Ocimum basilicum var. thyrsiflora (Thai basil) aqueous extract against stimulated F. oxysporum was studied in vivo. The presoaked tomato seeds with yeast-treated and untreated O. basilicum var. thyrsiflora extracts were cultivated in F. oxysporum-infused soil. This part investigated the recovery role of these botanical extracts against the Fusarium infection on tomato plants, especially on its growth and biochemical traits. The research showed that the vegetative and floral growth parameters of plant decreased significantly due to F. oxysporum infection. The pigment contents, including carotenoids, β-carotene and lycopene in tomato fruits, were also passively affected by fungus infection at variance to phenolic and flavonoid content. Moreover, the O. basilicum var. thyrsiflora extract presoaked seeds remarkably enhanced the growth parameters of plant and the fruit pigment content. There was no significant difference in fungus infection recovery between infected plants that got yeast-treated extract and infected plants that got yeast-untreated extract. However, the pathogen inhibition percentage with extract from yeast-treated Thai basil plants in vitro increased. This research showed that utilizing O. basilicum var. thyrsiflora extract to control F. oxysporum infection of tomato plants was possible and available.