Growing evidence recommends that radiofrequency radiations might be a new type of environmental pollutant. The consequences of RFR on the human immune system have gained considerable interest in recent years, not only to examine probable negative effects on health but also to understand if RFR can modulate the immune response positively. Although several studies have been published on the immune effects of RFR but no satisfactory agreement has been reached. Hence this review aims to evaluate the RFR modulating impacts on particular immune cells contributing to various innate or adaptive immune responses. In view of existing pieces of evidence, we have suggested an intracellular signaling cascade responsible for RFR action. The bio-effects of RFR on immune cell morphology, viability, proliferation, genome integrity, and immune functions such as ROS, cytokine secretion, phagocytosis, apoptosis, etc. are discussed. The majority of existing evidence point toward the possible shifts in the activity, number, and/or function of immunocompetent cells, but the outcome of several studies is still contradictory and needs further studies to reach a conclusion. Also, the direct association of experimental studies to human risks might not be helpful as exposure parameters vary in real life. On the basis of recent available literature, we suggest that special experiments should be designed to test each particular signal utilized in communication technologies to rule out the hypothesis that longer exposure to RFR emitting devices would affect the immunity by inducing genotoxic effects in human immune cells.

Here, we examined the combinational effect of ocean acidification (OA) and mercury (Hg) in the planktonic copepod Pseudodiaptomus annandalei in cross-factored response to different pCO₂ (400, 800 μatm) and Hg (control, 1.0 and 2.5 μg/L) exposures for three generations (F0–F2), followed by single-generation recovery (F3) under clean condition. Several phenotypic traits and Hg accumulation were analyzed for F0–F3. Furthermore, shotgun-based quantitative proteomics was performed for F0 and F2. Our results showed that OA insignificantly influenced the traits. During F0–F2, combined exposure reduced Hg accumulation as compared with the counterpart Hg treatment, supporting the mitigating effect of OA on Hg toxicity in copepods. Proteomics analysis indicated that the copepods probably increased energy production/storage and stress response to ensure physiological resilience against OA. However, Hg induced many toxic events (e.g., energy depletion and degenerated organomorphogenesis/embryogenesis for F0; cell cycle arrest and detrimental stress-defense for F2), which were translated to the population-level adverse outcome, i.e., compromised growth/reproduction. Particularly, compensatory proteome response was identified (e.g., increased immune defense for F0; energetic compensation and enhanced embryogenesis for F2), accounting for a negative interaction between OA and Hg. Together, this study provides the molecular mechanisms behind the effects of OA and Hg pollution in marine copepods.

Tributyltin (TBT) is a widely used organotin compound around the world and was frequently detected in surface waters, which would pose risk to aquatic organisms. However, the mechanisms of TBT-induced toxicity is not full clear. The present study investigated the effects of the tributyltin (TBT) on the blood parameters, immune responses and thyroid hormone system in zebrafish. Fish were exposed to sublethal concentrations of TBT (10 ng/L, 100 ng/L and 300 ng/L) for 6 weeks. The effects of long-term exposure to TBT on blood parameters (NH3, ammonia; GLU, glucose; TP, total proteins; CK, creatine kinase; ALT, alanine aminotransferase; AST, aspartate aminotransferase), immune responses (Lys, lysozyme; IgM, immunoglobulin M) and some indexes related thyroid hormone system (T3, 3,5,3′-triiodothyronine; T4, thyroxine) were measured in zebrafish, as well as the expression of genes related to immune responses and thyroid hormone system. Based on the results, the physiological-biochemical responses was significantly enhanced with an increase in TBT concentration, reflected by the abnormal blood indices, dysregulation of endocrine system and immunotoxicity in zebrafish under TBT stress. The present study greatly extends our understanding of adverse effects of TBT on aquatic organisms.

Nitrate is a major pollutant component in ambient PM₂.₅. It is known that chronic exposure to PM₂.₅ NO₃⁻ damages respiratory functions. We aim to explore the underlying toxicological mechanism at single cell resolution.We systematically conducted exposure experiments on forty C57BL/6 mice, assessed respiratory functions, and profiled lung transcriptome. . Afterward, we estimated the cell type compositions from RNA-seq data using deconvolution analysis. The genes and pathways associated with respiratory function and dysregulated by to PM₂.₅ NO₃⁻ exposure were characterized at bulk-tissue and single-cell resolution.PM₂.₅ NO₃⁻ exposure did not significantly modify the cell type composition in lung, but profoundly altered the gene expression within each cell type. At ambient concentration (22 μg/m³), exposure significantly (FDR<10%) altered 95 genes’ expression. Among the genes associated with respiratory functions, a large fraction (74.6–91.7%) were significantly perturbed by PM₂.₅ NO₃⁻ exposure. For example, among the 764 genes associated with peak expiratory flow (PEF), 608 (79.6%) were affected by exposure (p = 1.92e-345). Pathways known to play role in lung disease pathogenesis, including circadian rhythms, sphingolipid metabolism, immune response and lysosome, were found significantly associated with respiratory functions and disrupted by PM₂.₅ NO₃⁻ exposure.This study extended our knowledge of PM₂.₅ NO₃⁻ exposure’s effect to the levels of lung gene expression, pathways, lung cell type composition and cell specific transcriptome. At single cell resolution, we provided insights in toxicological mechanism of PM₂.₅ NO₃⁻ exposure and subsequent pulmonary disease risks.

The residue of simazine herbicide in the environment is known as one of pollutant stress for lizards by crippling its fitness on direct toxic effects and indirect food shortage via the food chain effects. Both stressors were considered in our experiment in the simazine exposure and food availability to lizards (Eremias argus). The results revealed that starvation significantly reduced the lizard’s energy reserve and native immune function, while the accumulation of simazine in the liver was significantly increased. Simazine caused oxidative stress in the liver of lizards, but oxidative damage only occurred in the starved lizards. Simazine also changed the energy reserves, native immune function and detoxification of well-fed lizards, while the starved lizards showed different sensitivity to simazine. Simazine or starvation treatment independently activated the lizard HPA axis, but co-treatment caused the HPA axis inhibition. Besides, according to the variations on amino acid neurotransmitters, corticosterone hormone and thermoregulatory behavior, we inferred that lizards in threatens take the appropriate strategy on energy investment and allocation through neural, endocrine and behavioral pathways to maximize benefits in dilemma. Energy allocation was necessary, while suppression on any physiological process comes at a cost that is detrimental to long-term individual fitness.

As ubiquitous, persistent organic pollutants, polycyclic aromatic hydrocarbons (PAHs) have adverse impacts on human health. Phenanthrene (Phe) is one of the most abundant PAHs in the environment. However, the long-term effects of exposure to environmental level of Phe on the kidneys and the potential mechanisms are unclear. T helper (Th) cells, a subtype of CD4⁺ T cells that play a central role in the renal immune microenvironment. In this study, male mice were chronically exposed to 5, 50, and 500 ng/kg bw Phe every other day for total 210 days. Those results indicated that environmental Phe exposure caused kidney hypertrophy, injury and fibrosis in the mice. Chronic, long-term environmental level of Phe exposure did not significantly alter the innate immune response but induced adaptive immune response changes (Th1/Th2 related cytokines release), causing a type 1 immune response in the 5 ng/kg bw Phe group and a type 2 immune response in the high dose groups (50 and 500 ng/kg bw). This study provides novel insights into the roles of adaptive immune response in long-term PAH exposure-induced chronic kidney injury and fibrosis, which is beneficial for further understanding the potential health hazards of PAHs and providing new avenues for immune intervention strategies to alleviate PAHs toxicity.

The prevalence of microplastic debris in aquatic ecosystems as a result of anthropogenic activity has received worldwide attention. Although extensive research has reported ubiquitous and directly adverse effects on organisms, only a few published studies have proposed the long-term ecological consequences. The research in this field still lacks a systematic overview of the toxic effects of microplastics and a coherent understanding of the potential ecological consequences. Here, we draw upon cross-disciplinary scientific research from recent decades to 1) seek to understand the correlation between the responses of organisms to microplastics and the potential ecological disturbances, 2) summarize the potential ecological consequences triggered by microplastics in aquatic environments, and 3) discuss the barriers to the understanding of microplastic toxicology. In this paper, the physiochemical characteristics and dynamic distribution of microplastics were related to the toxicological concerns about microplastic bioavailability and environmental perturbation. The extent of the ecological disturbances depends on how the ecotoxicity of microplastics is transferred and proliferated throughout an aquatic environment. Microplastics are prevalent; they interfere with nutrient productivity and cycling, cause physiological stress in organisms (e.g., behavioral alterations, immune responses, abnormal metabolism, and changes to energy budgets), and threaten the ecosystem composition and stability. By integrating the linkages among the toxicities that range from the erosion of individual species to the defective development of biological communities to the collapse of the ecosystem functioning, this review provides a bottom-up framework for future research to address the mechanisms underlying the toxicity of microplastics in aquatic environments and the substantial ecological consequences.

Harbor porpoises (Phocoena phocoena) in the North and Baltic Seas are exposed to anthropogenic influences including acoustic stress and environmental contaminants. In order to evaluate immune responses in healthy and diseased harbor porpoise cells, cytokine expression analyses and lymphocyte proliferation assays, together with toxicological analyses were performed in stranded and bycaught animals as well as in animals kept in permanent human care. Severely diseased harbor porpoises showed a reduced proliferative capacity of peripheral blood lymphocytes together with diminished transcription of transforming growth factor-β and tumor necrosis factor-α compared to healthy controls. Toxicological analyses revealed accumulation of polychlorinated biphenyls (PCBs), dichlorodiphenyldichloroethylene (DDE), and dichlorodiphenyltrichloroethane (DDT) in harbor porpoise blood samples. Correlation analyses between blood organochlorine levels and immune parameters revealed no direct effects of xenobiotics upon lymphocyte proliferation or cytokine transcription, respectively. Results reveal an impaired function of peripheral blood leukocytes in severely diseased harbor porpoises, indicating immune exhaustion and increased disease susceptibility.

Epidemiological evidence suggests that phthalate plasticizers may act as “obesogens”, which are chemicals that exacerbate obesity. The gastrointestinal (GI) system is the primary exposure route for phthalates, however, the relationship between phthalate-driven perturbations of GI system functions that can influence obesity has yet to be examined. To address this knowledge gap, we exposed Danio rerio (zebrafish) for 60 days to either (1) Control feeding (5 mg/fish/day), (2) Overfeeding (20 mg/fish/day) or (3) Overfeeding with diethyl-hexyl phthalate (DEHP) (20 mg/fish/day with 3 mg/kg DEHP). After 60 days, Overfed and Overfed + DEHP zebrafish had elevated body mass, and hepatosomatic and gonadosomatic indices. RNAseq analysis of the GI revealed enrichment of gene networks related to lipid metabolism in the Overfed + DEHP group. Many of the enriched networks were under transcriptional control of peroxisome proliferator activated receptor alpha (pparα), a known modulator of lipid metabolism, immune function, and GI function. Real-time PCR confirmed that pparα was overexpressed in the Overfed + DEHP zebrafish, further revealing a pathway by which DEHP may influence lipid metabolism via the GI. These data increase our understanding of phthalate-driven effects on GI function and lipid metabolism, identifying gut-specific gene networks that may drive phthalate-exacerbated obesity.

Phthalates are widely used as plasticizers that influence sexual and reproductive development. Here, we investigated whether di-(2-ethylhexyl) phthalate (DEHP) affects macrophage polarization that are associated with tumor initiation and progression. No changes were observed in LPS- or ConA-stimulated in vitro spleen B or T cell proliferation for 48 h, respectively. In contrast, macrophage functions were inhibited in response to DEHP for 12 h as judged by LPS-induced H₂O₂ and NO production and zymosan A-mediated phagocytosis. When six weeks old male mice were pre-exposed to 4.0 mg/kg DEHP for 21 days before the injection of B16F10 melanoma cells and post-exposed to 4.0 mg/kg DEHP for 7 days, tumor nodule formation and the changes in tumor volume were higher than those in control group. Furthermore, when male mice were intraperitoneally pretreated with DEHP for 3 or 4 weeks and peritoneal exudate cells (PECs) or bone marrow-derived macrophages (BMDMs) were incubated with lipopolysaccharide (LPS), the expression of COX-2, TNF-α, and IL-6 was reduced in DEHP-pretreated cells as compared with that in LPS-stimulated control cells. While the production of nitric oxide (NO) for 18 h was reduced by LPS-stimulated PECs and M1-type BMDMs, IL-4 expression was enhanced in LPS-stimulated BMDMs. When BMDMs were incubated with IL-4 for 30 h, arginase 1 for M2-type macrophages was increased in transcriptional and translational level. Data implicate that macrophages were differentially polarized by DEHP treatment, which reduced M1-polarzation but enhanced M2-polarization. Taken together, these data demonstrate that DEHP could affect in vivo immune responses of macrophages, leading to the suppression of their tumor-preventing ability. This suggests that individuals at high risk for tumor incidence should avoid long-term exposure to various kind of phthalate including DEHP.