**1. Introduction**

With the deterioration of the environment and the growth of the population, a good public health environment and adequate food supplies have increasingly become stumbling blocks for the development of human society [1–3]. Pesticides play an important role in controlling insect-borne diseases and developing agricultural production [2,4,5]. The ideal pesticide is effective against targeted diseases and insect pests without harming the human body; however, this seems difficult to achieve [6]. Mounting evidence has shown that pesticide residues can impact human health through environmental and food contamination [2], even at very low levels of exposure [4]. Therefore, a comprehensive understanding of pesticide toxicities is essential to the rational application of pesticides.

Numerous pesticide toxicity assessments have been carried out in recent years, but most of them are focused on general toxicity (acute toxicity, subchronic or subacute toxicity, chronic toxicity, etc.), endocrine toxicity, neurotoxicity, and "mutagenesis, carcinogenesis, teratogenesis" effects [7–10]. However, when a chemical compound is stated to be toxic, it does not necessarily mean that it induces the death of cells; effects may not result in cytotoxicity but alteration of cell function, leading to a detrimental outcome [11]. Among them, the immune system is the first line of defense against foreign hazardous chemicals within the human body. Thus, the immune response triggered by pesticides may be closely associated with the

**Citation:** Li, Y.-C.; Liu, S.-Y.; Meng, F.-B.; Xu, S.-H.; Qiu, J.; Qian, Y.-Z.; Xu, Y.-Y.; Li, Y. Comparative Transcriptome Analysis to Investigate the Immunotoxicity Mechanism Triggered by Dimethomorph on Human Jurkat T Cell Lines. *Foods* **2022**, *11*, 3848. https://doi.org/10.3390/ foods11233848

Academic Editor: Susana Casal

Received: 15 September 2022 Accepted: 24 November 2022 Published: 28 November 2022

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predisposition to different types of disease because the immune system mutually and closely interacts with all body organs [12,13]. Therefore, immunotoxicity evaluations of pesticide residues are very important for a comprehensive pesticide residue risk assessment that can guide agricultural production. Traditional immunotoxicity is usually evaluated through animal experiments for studying the specific antigen immune response, immune function, and so on. However, animal experiments are time consuming and require a lot of animal materials, and the use of animals is an important ethical and political issue [14]. Therefore, animal alternative methods (such as in vitro cell experiment) combined with bioinformatics has the potential to provide more comprehensive knowledge on the toxicological mechanism of chemicals in biological systems than more traditional approaches [15].

Dimethomorph (4-[3-(4-chlorophenyl)-3-(3-4-dimethox-yphenyl) acryloyl] morpholine, DMM), a cinnamic acid derivative, is a broad-spectrum fungicide globally used in agricultural production to prevent gray mold, powdery and downy mildews, crown and root rots, and late blight [16,17]. Since the use of DMM is very extensive, some reports in recent years have shown that the content of water, soil, and agricultural products of DMM range from ng/kg to mg/kg [18] and pose a certain risk to living organisms, including aquatic organisms, birds, and mammals [19,20]. Therefore, numerous studies have been performed to determine the dissipation and residue of DMM in vegetables, fruits, and their processed products [19–22]. More importantly, many studies have demonstrated that DMM is toxic to some soil and water microflora, birds, and mammals, even at very low concentrations [18,20]. Although the Environmental Protection Agency (EPA) reports show that DMM has low toxicity to humans, there has been insufficient knowledge regarding the toxicity and toxicity mechanisms of DMM pesticides in humans, especially immunotoxicity. In addition, owing to the continual and prolonged exposure of dimethomorphs, previous studies have indicated that fungal species have developed resistance and become insensitive to lower concentrations of DMM [16]. In order to fight fungal infection, a higher concentration of DMM is sprayed in fields, resulting in an increase in residues within agricultural products, as high as 7 mg/kg, which has been detected in vegetables. Meanwhile, a previous study also suggested that DMM is extremely resistant to hydrolysis and has a long half-life in the ecosystem [18]. Therefore, it is necessary to study the toxicity and mechanism of DMM in order to provide some reference for its risk assessment.

In the present study, the in vitro immunotoxicity of DMM in humans was investigated by using the human Jurkat T cell line, an in vitro model system frequently used in immunotoxicity evaluation due to its well-established reliability [23]. In addition, a comparative transcriptome analysis was applied to reveal the underlying immunotoxicity mechanism of DMM. To our knowledge, this is the first study to focus on the immunotoxicity of DMM to human immune cells, and the results provide a reference for the risk assessment of DMM.
