Correction: TGFβ-activation by dendritic cells drives Th17 induction and intestinal contractility and augments the expulsion of the parasite Trichinella spiralis in mice

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.

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Trichinella spiralis paramyosin activates mouse bone marrow-derived dendritic cells and induces regulatory T cells

Parasites & Vectors ◽

10.1186/s13071-016-1857-y ◽

2016 ◽

Vol 9 (1) ◽

Cited By ~ 9

Author(s):

Kai Guo ◽

Ximeng Sun ◽

Yuan Gu ◽

Zixia Wang ◽

Jingjing Huang ◽

...

Keyword(s):

Bone Marrow ◽

T Cells ◽

Dendritic Cells ◽

Regulatory T Cells ◽

Trichinella Spiralis ◽

Mouse Bone Marrow

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Glutathione-S-transferase of Trichinella spiralis regulates maturation and function of dendritic cells

Parasitology ◽

10.1017/s003118201900115x ◽

2019 ◽

Vol 146 (14) ◽

pp. 1725-1732 ◽

Cited By ~ 3

Author(s):

Xuemin Jin ◽

Yong Yang ◽

Xiaolei Liu ◽

Haining Shi ◽

Xuepeng Cai ◽

...

Keyword(s):

T Cells ◽

Dendritic Cells ◽

Cellular Response ◽

Trichinella Spiralis ◽

Detoxification Enzymes ◽

Glutathione S Transferase ◽

Mhc Ii ◽

The Family ◽

And Function ◽

Pro Inflammatory Cytokines

AbstractImmunomodulation by molecules from Trichinella spiralis (T. spiralis) has been widely reported. Glutathione-S-transferase (GST) is a major immune-modulator of the family of detoxification enzymes. Dendritic cells (DCs) are an important target for the regulation of the immune response by T. spiralis. In this study, the recombinant GST of T. spiralis (rTs-GST) was expressed and purified. rTs-GST induced low CD40 expression and moderate CD80, CD86 and MHC-II expressions and inhibited the increase of CD40, CD80 and CD86 on DCs induced by LPS. We showed that rTs-GST decreased the LPS-induced elevated level of pro-inflammatory cytokines of DCs and enhanced the level of regulatory cytokines IL-10 and TGF-β. Furthermore, co-culture of DCs and CD4+ T cells demonstrated that rTs-GST-treated DCs suppressed the proliferation of OVA-specific CD4+ T cells and increased the population of regulatory T cells (Tregs). rTs-GST-treated DCs induced a higher level of IL-4, IL-10 and TGF-β, but inhibited the level of IFN-γ. This indicates that rTs-GST-pulsed DCs induce both Th2-type responses and Tregs. These findings contribute to the current understanding of the immunomodulation of Ts-GST on cellular response and immunomodulation of T. spiralis.

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DC-SIGN signalling induced by Trichinella spiralis products contributes to the tolerogenic signatures of human dendritic cells

Scientific Reports ◽

10.1038/s41598-020-77497-x ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Jelena Cvetkovic ◽

Nataša Ilic ◽

Alisa Gruden-Movsesijan ◽

Sergej Tomic ◽

Ninoslav Mitic ◽

...

Keyword(s):

Dendritic Cells ◽

Trichinella Spiralis ◽

T Cell Response ◽

Toll Like Receptor ◽

Tolerogenic Dendritic Cells ◽

Toll Like Receptor 2 ◽

Secretory Products ◽

Human Dendritic Cells ◽

First Time

AbstractTolerogenic dendritic cells (tolDCs) are central players in the maintenance of immune tolerance and thereby have been identified as the most favourable candidates for cell therapy of autoimmune diseases. We have recently shown that excretory-secretory products (ES L1) released by Trichinella spiralis larvae induce stable human tolDCs in vitro via Toll-like receptor 2 (TLR2) and TLR4. However, engagement of these receptors did not fully explain the tolerogenic profile of DCs. Here, we observed for the first time that dendritic cell-specific ICAM-3 grabbing non-integrin (DC-SIGN) interacts with highly glycosylated ES L1 and contributes to the generation of ES L1-induced tolDCs. Blocking DC-SIGN interfered with the ES L1-induced higher expression of CD40 and CCR7 and the production of IL-10 and TGF-β by DCs. The cooperation of TLR2, TLR4 and DC-SIGN receptors is of importance for the capacity of DCs to prime T cell response toward Th2 and to induce expansion of CD4+CD25+Foxp3+ T cells, as well as for the production of IL-10 and TGF-β by these cells. Overall, these results indicate that induction of tolDCs by ES L1 involves engagement of multiple pattern recognition receptors namely, TLR2, TLR4 and DC-SIGN.

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Ts-Hsp70 induces protective immunity against Trichinella spiralis infection in mouse by activating dendritic cells through TLR2 and TLR4

PLoS Neglected Tropical Diseases ◽

10.1371/journal.pntd.0006502 ◽

2018 ◽

Vol 12 (5) ◽

pp. e0006502 ◽

Cited By ~ 7

Author(s):

Rui Zhang ◽

Qing Sun ◽

Yi Chen ◽

Ximeng Sun ◽

Yuan Gu ◽

...

Keyword(s):

Dendritic Cells ◽

Protective Immunity ◽

Trichinella Spiralis

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Heat shock protein 70 from Trichinella spiralis induces protective immunity in BALB/c mice by activating dendritic cells

Vaccine ◽

10.1016/j.vaccine.2014.06.055 ◽

2014 ◽

Vol 32 (35) ◽

pp. 4412-4419 ◽

Cited By ~ 20

Author(s):

Lei Fang ◽

Liang Sun ◽

Jing Yang ◽

Yuan Gu ◽

Bin Zhan ◽

...

Keyword(s):

Dendritic Cells ◽

Heat Shock ◽

Heat Shock Protein ◽

Heat Shock Protein 70 ◽

Protective Immunity ◽

Trichinella Spiralis

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Application of dendritic cells stimulated with Trichinella spiralis excretory–secretory antigens alleviates experimental autoimmune encephalomyelitis

Medical Microbiology and Immunology ◽

10.1007/s00430-012-0286-6 ◽

2013 ◽

Vol 202 (3) ◽

pp. 239-249 ◽

Cited By ~ 47

Author(s):

Lj. Sofronic-Milosavljevic ◽

I. Radovic ◽

N. Ilic ◽

I. Majstorovic ◽

J. Cvetkovic ◽

...

Keyword(s):

Dendritic Cells ◽

Experimental Autoimmune Encephalomyelitis ◽

Trichinella Spiralis ◽

Autoimmune Encephalomyelitis ◽

Experimental Autoimmune

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Trichinella spiralis Excretory–Secretory Products Induce Tolerogenic Properties in Human Dendritic Cells via Toll-Like Receptors 2 and 4

Frontiers in Immunology ◽

10.3389/fimmu.2018.00011 ◽

2018 ◽

Vol 9 ◽

Cited By ~ 19

Author(s):

Nataša Ilic ◽

Alisa Gruden-Movsesijan ◽

Jelena Cvetkovic ◽

Sergej Tomic ◽

Dragana Bozidar Vucevic ◽

...

Keyword(s):

Dendritic Cells ◽

Trichinella Spiralis ◽

Toll Like Receptors ◽

Secretory Products ◽

Human Dendritic Cells

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Trichinella spiralis Excretory–Secretory Products Stimulate Host Regulatory T Cell Differentiation through Activating Dendritic Cells

Cells ◽

10.3390/cells8111404 ◽

2019 ◽

Vol 8 (11) ◽

pp. 1404 ◽

Cited By ~ 4

Author(s):

Sun ◽

Guo ◽

Hao ◽

Zhan ◽

Huang ◽

...

Keyword(s):

Dendritic Cells ◽

T Cell ◽

Regulatory T Cell ◽

Trichinella Spiralis ◽

Treg Cells ◽

Chronic Infections ◽

Cell Responses ◽

Muscle Larvae ◽

Secretory Products

Trichinella spiralis maintains chronic infections within its host, involving a variety of immunomodulatory properties, the mechanisms of which have not been completely elucidated. In this study, we found that T. spiralis infection induced strong regulatory T cell responses through parasite excretory–secretory (ES) products, characterized by increase of CD4+CD25+Foxp3+ and CD4+CD25−Foxp3+ Treg cells accompanied by high levels of IL-10 and TGF-β. T. spiralis adult worm excretory–secretory products (AES) and muscle larvae excretory–secretory products (MES) were both able to activate BMDCs in vitro to facilitate their maturation and to create regulatory cytokines IL-10 and TGF-β. The T. spiralis AES- and MES-pulsed dendritic cells (DCs) possessed abilities not only to present antigens to sensitized CD4+ T cell to stimulate their proliferation but also to induce naive CD4+ T cells to differentiate to Treg cells secreting IL-10 and TGF-β. The passive transfer of T. spiralis AES- and MES-pulsed bone marrow-derived dendritic cells (BMDCs) conferred the naive mice to acquire the differentiation of Treg cells. T. spiralis AES possesses a better ability to induce Treg cells than did MES, although the latter has the ability to induce CD4+CD25−Foxp3+ Treg cells. The results obtained in this study suggested that T. spiralis ES products stimulate the differentiation of host Treg cells possibly through activating dendritic cells to create a regulatory environment that benefits the survival of the parasite in the host.

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