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

Zhang, Rui; Sun, Qing; Chen, Yi; Sun, Xiaotao; Gu, Yuan; Zhang, Zhao; Cheng, Yue; Zhao, Limei; Huang, Jingjing; Zhan, Bin; Zhu, Xiaoyan

doi:10.1371/journal.pntd.0006502

Cited by 23 publications

(18 citation statements)

References 54 publications

(57 reference statements)

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“…Hsp70 has been previously described to influence innate immunity and inflammatory responses. 293 It has been believed that hepatocyte is devoid of innate immunities. Ma et al reported that the expression of Grp78 is stimulated by HBV replication.…”

Section: The Function Of Hsp70 Family In Virus Infectionmentioning

confidence: 99%

“…299 Aside from the anti-inflammation function of intracellular Hsp70, the secreted extracellular Hsp70 binds to dendritic cells and macrophages before being recognized by its binding elements, most of which are innate immune receptors. 293,300 Toll-like receptors (TLRs) detect virus invasion and immediately trigger intracellular innate antiviral response. 301 They belong to type I integral membrane glycoproteins of IL-1 receptor (IL-1R) superfamily.…”

Section: The Function Of Hsp70 Family In Virus Infectionmentioning

confidence: 99%

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Stress proteins: the biological functions in virus infection, present and challenges for target-based antiviral drug development

Wan

Song

et al. 2020

Sig Transduct Target Ther

109

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Stress proteins (SPs) including heat-shock proteins (HSPs), RNA chaperones, and ER associated stress proteins are molecular chaperones essential for cellular homeostasis. The major functions of HSPs include chaperoning misfolded or unfolded polypeptides, protecting cells from toxic stress, and presenting immune and inflammatory cytokines. Regarded as a double-edged sword, HSPs also cooperate with numerous viruses and cancer cells to promote their survival. RNA chaperones are a group of heterogeneous nuclear ribonucleoproteins (hnRNPs), which are essential factors for manipulating both the functions and metabolisms of pre-mRNAs/hnRNAs transcribed by RNA polymerase II. hnRNPs involve in a large number of cellular processes, including chromatin remodelling, transcription regulation, RNP assembly and stabilization, RNA export, virus replication, histonelike nucleoid structuring, and even intracellular immunity. Dysregulation of stress proteins is associated with many human diseases including human cancer, cardiovascular diseases, neurodegenerative diseases (e.g., Parkinson's diseases, Alzheimer disease), stroke and infectious diseases. In this review, we summarized the biologic function of stress proteins, and current progress on their mechanisms related to virus reproduction and diseases caused by virus infections. As SPs also attract a great interest as potential antiviral targets (e.g., COVID-19), we also discuss the present progress and challenges in this area of HSP-based drug development, as well as with compounds already under clinical evaluation.

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Section: The Function Of Hsp70 Family In Virus Infectionmentioning

confidence: 99%

Section: The Function Of Hsp70 Family In Virus Infectionmentioning

confidence: 99%

Stress proteins: the biological functions in virus infection, present and challenges for target-based antiviral drug development

Wan

Song

et al. 2020

Sig Transduct Target Ther

109

View full text Add to dashboard Cite

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“…Intestinal adult worms were collected at 7 dpi, and muscle larvae were recovered and counted at 35 dpi as previously described [27]. The protective immunity was calculated based on the percent of reduction in the mean number of adult worms or the recovered muscle larvae per gram (LPG) of muscle from vaccinated groups compared with PBS group.…”

Section: Parasite Burden Assessmentsmentioning

confidence: 99%

Lentinan improved the efficacy of vaccine against Trichinella spiralis in an NLRP3 dependent manner

et al. 2020

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There is an urgent need for the development of new, improved vaccine adjuvants against T. spiralis infection. Polysaccharides are effective, safe, and biodegradable as adjuvant. In our study, we first observed the protective efficacy of lentinan as adjuvant against helminth T. spiralis infection. Recombinant T. spiralis Serpin (rTs-Serpin) immunoscreened from a cDNA library of T. spiralis, as a vaccine, protect host against Trichinella infection. The reduction rate of helminth burden of rTs-Serpin+lentinan-immunized mice was significantly increased compared with rTs-Serpin+FCA-immunized mice. rTs-Serpin+lentinan induced IgG1-dominant immune response and higher levels of IFN-γ and IL-4. rTs-Serpin+lentinan displayed a lower reduction rate of parasite burden in NLRP3-/mice than that in WT mice and lower level of IgG1 than that in WT mice. The level of IL-4, but not IFN-γ, from NLRP3-/mice immunized by rTs-Serpin+lentinan was significantly lower than that from WT mice, suggesting that NLRP3 is associated with rTs-Serpin+lentinan-triggering Th2 protective immunity against T. spiralis infection. In summary, we revealed that lentinan was a novel adjuvant against T. spiralis infection via NLRP3. NLRP3 therefore represents an important target for adjuvant discovery and the control of T. spiralis infection.

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“…WT and NLRP3 −/− mice were infected with 300 muscle larvae (ML). MLs were recovered and counted at 35 dpi as previously described [16]. Briefly, the muscle tissues of infected mice were cut into pieces and digested by pepsin hydrochloric digestive fluid.…”

Section: Larvae Burden Assessmentsmentioning

confidence: 99%

NLRP3 played a role in Trichinella spiralis-triggered Th2 and regulatory T cells response

Jin

Bai

Yang

et al. 2020

Vet Res

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Trichinella spiralis maintains chronic infections within its host. Muscle larvae excretory-secretory products (MLES) typically induce parasite-specific immune responses such as the Th2 response and regulatory T cells (Tregs) by modulating dendritic cell (DC) phenotype via the recognition of pattern recognition receptors (PRRs), such as Nod-like receptors (NLRs). We aimed to investigate the role of NLRP3 in T. spiralis-triggered immune response. We found that larvae burden was increased in NLRP3 −/− mice compared to wild type (WT) mice. Administration of MLES induced higher levels of IL-4, IL-10, TGF-β and population of Tregs in WT mice than in NLRP3 −/− mice. In vitro, we showed that increased expression of CD40 on the surface of MLES-treated DCs was inhibited after NLRP3 knockout. Increased production of IL-1β, IL-18, IL-10 and TGF-β, but not IL-12p70, was significantly diminished in the absence of NLRP3. Furthermore, our results demonstrated that MLES-treated DCs induced higher levels of IL-4, IL-10 and TGF-β and populations of Tregs in vitro. These inductions were abolished by NLRP3 deficiency in DCs, suggesting that NLRP3 in MLES-treated DCs plays a role in promoting the Th2 and Treg response. Taken together, we identified for the first time the involvement of NLRP3 in host defences against T. spiralis.

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

Cited by 23 publications

References 54 publications

Stress proteins: the biological functions in virus infection, present and challenges for target-based antiviral drug development

Stress proteins: the biological functions in virus infection, present and challenges for target-based antiviral drug development

Lentinan improved the efficacy of vaccine against Trichinella spiralis in an NLRP3 dependent manner

NLRP3 played a role in Trichinella spiralis-triggered Th2 and regulatory T cells response

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