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

Sun, Xiaotao; Guo, Kai; Hao, Chunyue; Zhan, Bin; Huang, Jingjing; Zhu, Xiaoyan

doi:10.3390/cells8111404

Cited by 28 publications

(21 citation statements)

References 52 publications

(61 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is also identified that helminth-secreted proteins stimulated Treg response through up-regulating PD-1 in CD4 + T cells ( Cheng et al., 2018 ). A recent study also showed that helminth-derived proteins stimulated Treg differentiation through activating dendritic cells ( Sun et al., 2019b ). It is unknown if PD-1 or dendritic cells pathways are involved in the r Sj -Cys-initiated immunomodulation.…”

Section: Discussionmentioning

confidence: 99%

Schistosoma japonicum Cystatin Alleviates Sepsis Through Activating Regulatory Macrophages

Xie

Chen

et al. 2021

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

Multi-organ failure caused by the inflammatory cytokine storm induced by severe infection is the major cause of death for sepsis. Sj-Cys is a cysteine protease inhibitor secreted by Schistosoma japonicum with strong immunomodulatory functions on host immune system. Our previous studies have shown that treatment with Sj-Cys recombinant protein (rSj-Cys) attenuated inflammation caused by sepsis. However, the immunological mechanism underlying the immunomodulation of Sj-Cys for regulating inflammatory diseases is not yet known. In this study, we investigated the effect of Sj-Cys on the macrophage M2 polarization and subsequent therapeutic effect on sepsis. The rSj-Cys was expressed in yeast Pichia pastoris. Incubation of mouse bone marrow-derived macrophages (BMDMs) with yeast-expressed rSj-Cys significantly activated the polarization of macrophages to M2 subtype characterized by the expression of F4/80+ CD206+ with the elated secretion of IL-10 and TGF-β. Adoptive transfer of rSj-Cys treated BMDMs to mice with sepsis induced by cecal ligation and puncture (CLP) significantly improved their survival rates and the systemic clinical manifestations of sepsis compared with mice receiving non-treated normal BMDMs. The therapeutic effect of Sj-Cys-induced M2 macrophages on sepsis was also reflected by the reduced pathological damages in organs of heart, lung, liver and kidney and reduced serological levels of tissue damage-related ALT, AST, BUN and Cr, associated with downregulated pro-inflammatory cytokines (IFN-gamma and IL-6) and upregulated regulatory anti-inflammatory cytokines (IL-10 and TGF-β). Our results demonstrated that Sj-Cys is a strong immunomodulatory protein with anti-inflammatory features through activating M2 macrophage polarization. The findings of this study suggested that Sj-Cys itself or Sj-Cys-induced M2 macrophages could be used as therapeutic agents in the treatment of sepsis or other inflammatory diseases.

show abstract

Section: Discussionmentioning

confidence: 99%

Schistosoma japonicum Cystatin Alleviates Sepsis Through Activating Regulatory Macrophages

Xie

Chen

et al. 2021

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

show abstract

“…T. spiralis muscle larvae were isolated from the muscles of infected female ICR mice by a previously described method of modified pepsin-hydrochloric acid digestion ( Gu et al., 2013 ) as a source for infection. Each Wistar rat was orally infected with 12,000 muscle larvae of T. spiralis ( Martínez-Gómez et al., 2009 ; Sun et al., 2019b ) and the adult worms were collected from intestines of mice 106 hours post infection. The collected adult worms were washed with phosphate-buffered saline (PBS) for three times and then cultured in RPMI-1640 medium (Hyclone, Logan, UT, USA) supplemented with 100 U/mL penicillin and 100 µg/mL streptomycin (Gibco, Grand Island, NY, USA) at 37°C, 5% CO 2 for 48 h. The culture supernatant containing Ts -AES was collected and concentrated by centrifugating and buffer exchanged into PBS.…”

Section: Methodsmentioning

confidence: 99%

“…ES products derived from different developmental stages of T. spiralis may act different immunomodulatory effects ( Yang et al., 2014 ; Jin et al., 2019a ). Many experimental studies have shown that infection with T. spiralis or exposure to ES products of T. spiralis induced a strong Th2/Treg response correlated with the stimulation of anti-inflammatory cytokines (IL-4, IL-5, and IL-13) and regulatory cytokines (IL-10, TGF-β), as well as the inhibition of pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β) ( Han et al., 2019 ; Sun et al., 2019b ; Ding et al., 2020 ). T. spiralis ES has been successfully used for the treatment of inflammatory bowel diseases ( Yang et al., 2014 ; Jin et al., 2019a ; Wang Z. et al., 2020 ), allergic asthma ( Sun et al., 2019a ) and sepsis ( Du et al., 2014 ) in mouse models.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic Efficacy of Excretory-Secretory Products of Trichinella spiralis Adult Worms on Sepsis-Induced Acute Lung Injury in a Mouse Model

Qiu

Yang

et al. 2021

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

Acute lung injury (ALI) is a common complication of systemic inflammation or sepsis with high morbidity and mortality. Although many studies have confirmed that helminth-derived proteins had strong immunomodulatory functions and could be used to treat inflammatory diseases, there is no report on the therapeutic effect of excretory-secretory products of Trichinella spiralis adult worms (Ts-AES) on sepsis-induced ALI. In this study, the therapeutic efficacy of Ts-AES on sepsis-induced ALI and the underlying immunological mechanism and the signaling pathway were investigated. The results indicated that after being treated with Ts-AES, the survival rate of mice with CLP-induced sepsis was significantly increased to 50% for 72 hours after CLP surgery compared to PBS control group with all mice died. The sepsis-induced ALI was largely mitigated characterized by reduced inflammation cell infiltration and pathological changes in lung tissue, with decreased lung injury scores and lung wet/dry weight ratio. The therapeutic efficacy of Ts-AES is associated with stimulated Tregs response with increased regulatory cytokines IL-10 and TGF-β and downregulated pro-inflammatory cytokines (TNF-α, IL-6, IL-1β). The expression of HMGB1, TLR2 and MyD88 in lung tissue was inhibited after treatment of Ts-AES. Our results demonstrated that Ts-AES play an important role in immunomodulation and confer a therapeutic effect on sepsis-induced ALI through inhibiting pro-inflammatory cytokines. The activation of Tregs and increased level of regulatory cytokines IL-10 and TGF-β are possibly involved in the immunomodulatory functions of Ts-AES through HMGB1/TLR2/MyD88 signal pathway. The findings suggest Ts-AES is a potential therapeutic agent for prevention and treatment of sepsis-induced ALI and other inflammatory diseases.

show abstract

“…The excretory/secretory products (ESPs) of nematodes, trematodes and cestodes contain a wide range of molecules, including proteins, lipids, glycans, and nucleic acids, and they can aid in the penetration of host defensive barriers, the avoidance of the host immune response and establishment and survival in host tissues [45][46][47][48][49]. ESPs are also useful targets for investigating the interaction between parasitic helminths and hosts [50][51][52]. In studies on the ESPs of A. cantonensis, proteomic analysis has been employed to determine the composition of ESPs in adults.…”

Section: Discussionmentioning

confidence: 99%

Excretory/secretory products of Angiostrongylus cantonensis fifth-stage larvae induce endoplasmic reticulum stress via the Sonic hedgehog pathway in mouse astrocytes

Chen

Cheng

et al. 2020

Parasites Vectors

View full text Add to dashboard Cite

Background: Angiostrongylus cantonensis is an important food-borne zoonotic parasite. Humans are non-permissive hosts, and this parasite develops into fifth-stage larvae (L5) in the brain and subarachnoid cavity and then induces eosinophilic meningitis and eosinophilic meningoencephalitis. Excretory/secretory products (ESPs) are valuable targets for the investigation of host-parasite interactions. These products contain a wide range of molecules for penetrating defensive barriers and avoiding the immune response of the host. Endoplasmic reticulum (ER) stress has been found to be associated with a wide range of parasitic infections and inflammation. ER stress can increase cell survival via the activation of downstream signalling. However, the mechanisms of ER stress in A. cantonensis infection have not yet been clarified. This study was designed to investigate the molecular mechanisms of ER stress in astrocytes after treatment with the ESPs of A. cantonensis L5. Results: The results demonstrated that A. cantonensis infection activated astrocytes in the mouse hippocampus and induced the expression of ER stress-related molecules. Next, the data showed that the expression of ER stress-related molecules and the Ca 2+ concentration were significantly increased in activated astrocytes after treatment with the ESPs of L5 of A. cantonensis. Ultimately, we found that ESPs induced GRP78 expression via the Sonic hedgehog (Shh) signalling pathway. Conclusions: These findings suggest that in astrocytes, the ESPs of A. cantonensis L5 induce ER stress and that the Shh signalling pathway plays an important role in this process.

show abstract

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

Cited by 28 publications

References 52 publications

Schistosoma japonicum Cystatin Alleviates Sepsis Through Activating Regulatory Macrophages

Schistosoma japonicum Cystatin Alleviates Sepsis Through Activating Regulatory Macrophages

Therapeutic Efficacy of Excretory-Secretory Products of Trichinella spiralis Adult Worms on Sepsis-Induced Acute Lung Injury in a Mouse Model

Excretory/secretory products of Angiostrongylus cantonensis fifth-stage larvae induce endoplasmic reticulum stress via the Sonic hedgehog pathway in mouse astrocytes

Contact Info

Product

Resources

About