Excretory-secretory product of Trichinella spiralis inhibits tumor cell growth by regulating the immune response and inducing apoptosis.

The excretory-secretory product (ESP) of Trichinella spiralis (T. spiralis) has been reported to inhibit the growth of various tumor cells, but the mechanism is not yet clear. To explore the effect and mechanism of ESP on liver cancer cells, tumor models were established with H22 cells and then infected with T. spiralis. The results showed that the growth of tumors in mice infected with T. spiralis was significantly inhibited. ESP from adult worms or muscle larvae were then incubated with H22 cells in vitro, and it was found that the ESP could inhibit cell proliferation and promote apoptosis. Subsequently, apoptosis-related proteins in stimulated H22 cells were evaluated, and ESP was found to induce cell apoptosis through the mitochondrial pathway. Additionally, Th-related cytokines were investigated in vivo, and the results showed that the levels of Th1 cytokines were significantly increased in the early stage of T. spiralis infection, while Th2 cytokines increased later than Th1 cytokines, implying that Th1 cytokines with antitumor effects may play a role in inhibiting tumor growth at early stage. In short, ESP can directly induce tumor cell apoptosis and indirectly inhibit tumor cell growth through the host immune system, which may be the antitumor mechanism of T. spiralis infection.

The dynamics of select cellular responses and cytokine expression profiles in mice infected with juvenile Clonorchis sinensis.

Clonorchiasis is a zoonotic disease that can result in chronic infection in humans. The causative agent, Clonorchis sinensis (C. sinensis), is believed to primarily induce a Th2 immune response in infected mice. However, few studies have profiled host immune responses to C. sinensis infection during the juvenile phase. In the present study, the dynamics of select cellular responses and cytokine expression profiles during juvenile C. sinensis infection were investigated. The flow cytometry results showed that the CD4+ T cells percentage was significantly decreased between 12 days post-infection (dpi) and 24 dpi in the peripheral blood, and the CD8+ T cells percentage was significantly elevated after 3 dpi. The ratio of CD4+/CD8+ T cells was also significantly decreased after 3 dpi. Furthermore, we observed that the proportion of CD14+ monocyte-macrophages in the peripheral blood was significantly increased between 1 dpi and 12 dpi and peaked at 6 dpi. The percentage of classically activated macrophages (M1) and alternatively activated macrophages (M2) in the liver was significantly increased between 18 dpi and 30 dpi. qRT-PCR results showed that the expression levels of iNOS in the liver were significantly elevated after 3 dpi, and Arg-1 expression was significantly increased beginning at 12 dpi. ELISA results showed that the serum levels of the Th1 cytokines IFN-γ and IL-2 peaked at 6 dpi and decreased thereafter. Furthermore, the Th2 cytokines IL-4 and IL-13 began to be expressed and peaked at 24 dpi and 30 dpi, respectively. In addition, the levels of the Treg cytokines IL-10 and TGF-ß1 were significantly increased beginning at 6 dpi until 30 dpi. In the liver homogenate, the expression of IFN-γ, IL-2, and IL-4 mainly occurred before 6 dpi. IL-13 expression was significantly increased at 30 dpi. IL-10 and TGF-ß1 levels were significantly increased at 12 dpi and 24 dpi, and expression peaked at 24 dpi and 30 dpi, respectively. This study provides a fundamental characterization for the future analysis of host-parasite interactions and immune responses in hosts infected with juvenile C. sinensis.

Trichinella spiralis: inflammation modulator.

The hygiene hypothesis posits that the decreased incidence of parasitic infection in developed countries may underlie an increased prevalence of allergic and autoimmune diseases in these countries. As unique inflammation modulator of intracellular parasitism, Trichinella spiralis, or its excretory-secretory (ES) product, shows improved responses to allergies, autoimmune diseases, inflammatory bowel disease, type 1 diabetes, rheumatic arthritis and autoimmune encephalomyelitis by exerting immunomodulatory effects on both innate and adaptive immune cells in animal models. Research has shown that T. spiralis differs from other helminths in manipulation of the host immune response not only by well-known characteristics of its life cycle, but also by its inflammation modulation pathway. How the parasite achieves inflammation modulation has not been fully elucidated yet. This review will generalize the mechanism and focuses on ES immunomodulatory molecules of T. spiralis that may be important for developing new therapeutics for inflammatory disorders.

Murine hepatoma treatment with mature dendritic cells stimulated by Trichinella spiralis excretory/secretory products.

Excretory/Secretory Products (ESPs) of the nematode Trichinella spiralis contain antitumor-active substances that inhibit tumor growth. Mature dendritic cells (DCs) play a critical role in the antitumor immunity of the organism. As pathogen-derived products, it ought to be discussed whether T. spiralis ESPs will reduce the antitumor effect of mature DCs from the host before it is applied to patients' tumors. Therefore, the aim of this work was to evaluate the immunological effect of DCs stimulated by T. spiralis ESPs in H22 tumor-bearing mice. H22 tumor model mice in this study were randomly divided into four groups according to the treatment: PBS control group, ESP group, DCs group, and DCs stimulated with T. spiralis ESP (ESP+DCs group). The antitumor effect was evaluated by tumor inhibition rate and cytokine detection using ELISA. The results showed significant inhibition in tumor growth in the ESP+DCs, DCs and ESP groups when compared with the PBS control group (p < 0.01, p < 0.01, and p < 0.05, respectively). However, no significant difference was observed on tumor inhibition rates between the ESP+DCs and DCs groups. The decrease in IL-4, IL-6, and IL-10, and the increase in IFN-γ between the DCs and ESP+DCs groups were also not significant. Therefore, DCs stimulated by ESP did not reduce the antitumor effect of mature DCs, which demonstrated that the T. spiralis ESP would not affect the antitumor effect of mature DCs by modulating the immune response of the host, and that ESPs are safe in antitumor immunology when applied in a tumor model mice.

TITLE: Traitement des hépatomes murins avec des cellules dendritiques mûres stimulées par des produits d'excrétion-sécrétion de Trichinella spiralis. ABSTRACT: Les produits d'excrétion-sécrétion (PES) du nématode Trichinella spiralis contiennent des substances actives antitumorales qui inhibent la croissance tumorale. Les cellules dendritiques (CD) mûres jouent un rôle essentiel dans l'immunité anti-tumorale de l'organisme. En tant que produits dérivés d'agents pathogènes, il convient de déterminer si les PES de T. spiralis réduisent l'effet antitumoral des CD mûrs de l'hôte, avant leur application aux tumeurs des patients. Par conséquent, l'objectif de ce travail était d'évaluer l'effet immunologique des CD stimulées par les PES de T. spiralis chez des souris porteuses de tumeurs H22. Les souris modèles à tumeurs H22 dans cette étude ont été réparties au hasard en quatre groupes selon le traitement : groupe témoin PBS, groupe PES, groupe CD et groupe CD stimulés par les PES de T. spiralis (CD+PES). L'effet antitumoral a été évalué par le taux d'inhibition des tumeurs et la détection des cytokines en utilisant un dosage ELISA. Les résultats ont montré une inhibition significative de la croissance tumorale dans les groupes CD+PES, CD et PES par rapport au groupe témoin PBS (p < 0,01, p < 0,01 et p < 0,05, respectivement). Cependant, aucune différence significative n'a été observée sur le taux d'inhibition de la tumeur entre les groupes CD+PES et CD. La diminution de l'IL-4, de l'IL-6, de l'IL-10 et l'augmentation de l'IFN-γ entre les groupes CD et CD+PES n'étaient pas non plus significatives. Ainsi, les CD stimulées par les PES n'ont pas réduit l'effet antitumoral des CD mûrs, ce qui a démontré que les PES de T. spiralis n'affectaient pas l'effet antitumoral des CD mûrs en modulant la réponse immunitaire de l'hôte et que les PES sont sûrs en immunologie antitumorale quand ils sont appliqués à des souris modèles tumorales.

Effect of Trichinella spp. or derived antigens on chemically induced inflammatory bowel disease (IBD) in mouse models: A systematic review and meta-analysis.

OBJECTIVE: Trichinella or derived antigens have been suggested to be potential therapeutic agents for inflammatory bowel disease (IBD). We aimed to conduct a systematic review and meta-analysis of the available literature to estimate the effect of Trichinella or derived antigens on chemically induced IBD. METHODS: Studies were identified by searching the Cochrane Central Register of Controlled Trials, PubMed, Scopus, Web of Science, and Science Direct from inception to February 2020. We included articles written in English that investigated the effect of Trichinella infection and/or derived products in mouse models of IBD. Studies were pooled, and the combined standard mean difference (SMD) and 95% confidence interval (CI) were calculated using a random-effect or fixed-effect model. RESULTS: Thirteen studies were eventually included in the meta-analysis. The results indicated significant differences in the disease activity index (DAI), myeloperoxidase (MPO) activity, macroscopic inflammation score, and microscopic inflammation score between the experimental group and the control group. The anti-inflammatory cytokines interleukin (IL)-4, transforming growth factor-beta (TGF-ß), IL-10 and IL-13 were significantly increased in the experimental group compared with the control group, whereas the levels of the proinflammatory cytokines interferon (IFN)-γ, IL-6, TNF-α, and IL-17 were significantly decreased. The percentage of regulatory T (Treg) cells was also significantly increased, while the level of the M1 phenotypic macrophage marker iNOS was significantly decreased and the expression of the M2 phenotypic macrophage marker Arg-1 was significantly increased. CONCLUSION: Trichinella infection or derived antigens is effective for the alleviation of IBD in mouse models.

Label-free serum detection of Trichinella spiralis using surface-enhanced Raman spectroscopy combined with multivariate analysis.

Based on blood serum surface-enhanced Raman spectroscopy (SERS) analysis, this paper proposed a simple and unlabeled non-invasive serum detection for T. spiralis infection. Serum samples were collected and analyzed from 40 rats at 0 days post infection (dpi) (normal rats), 19 uninfected rats, and 16 rats infected with T. spiralis at 28 dpi, using SERS measurements. Multivariate statistical techniques, such as linear discriminant analysis (LDA) and principal components analysis (PCA), were used to analyze and identify the obtained blood serum SERS spectra. The diagnosis algorithms, based on PCA-LDA, achieved a diagnostic sensitivity of 87.5%, a specificity of 94.7%, and an accuracy of 91.4% for separating the samples infected with T. spiralis from the control samples. This exploratory study demonstrated that colloidal Ag NPs-based SERS serum analysis technique combined with PCA-LDA has a great potential in improving the detection of T. spiralis infection and onsite screening.

Acute shock caused by Clonorchis sinensis infection: a case report.

BACKGROUND: Clonorchiasis, caused by Clonorchis sinensis (C. sinensis) infection, is a serious food-borne zoonotic disease that is often asymptomatic or shows only mild symptoms, which leads to delayed treatment and chronic clonorchiasis and results in various complications, such as cholelithiasis, cholangitis, cholecystitis and cholangiocarcinoma. However, acute shock caused by C. sinensis infection has not been reported. Here, for the first time, we describe a fatal case of acute shock caused by C. sinensis infection. CASE PRESENTATION: A patient with a history of eating raw or undercooked freshwater fish was hospitalized with acute shock caused by severe abdominal pain. Physical examination suggested acute abdomen with severe abdominal pain and rigidity. Computed tomography (CT) detection indicated acute cholecystitis and cholelithiasis. After cholecystectomy, several liver flukes were found in the drainage tube. Furthermore, morphological analysis and polymerase chain reaction (PCR) identified the pathogen as C. sinensis. The liver gradually restored normal function after anthelmintic therapy with praziquantel. CONCLUSIONS: In this fatal case, C. sinensis infection was the cause of acute shock, which is rarely found in the clinic environment. This report aims to increase awareness of the hazards and complications related to clonorchiasis. The PCR diagnosis method used in this report might be helpful in reducing the misdiagnosis of clonorchiasis and unnecessary cholecystectomy.