Immunomodulatory effects of Trichinella spiralis excretory-secretory antigens on macrophages

Han, Caixia; Yu, Jie; Zhang, Ziqun; Zhai, Peng; Zhang, Yan; Meng, Shi; Yang, Yu; Li, Xiaoyun; Song, Mingxin

doi:10.1016/j.exppara.2018.10.001

Cited by 30 publications

(30 citation statements)

References 32 publications

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“…In contrast to filarial cystatins, rTsCstN did not induce the M2 macrophage phenotype, which could not increase regulatory cytokine and M2 marker levels [59]. As mentioned previously, TsES diminished the production of pro-inflammatory cytokines but promoted alternatively activated macrophage and regulatory cytokines productions both in vitro and in vivo [6,7,60]. These imply that the immunomodulatory properties of TsES may affect several molecules, including TsCstN, which need to be identified and characterized further soon.…”

Section: Discussionmentioning

confidence: 66%

“…However, there is ample evidence to indicate that macrophage functions are regulated by T. spiralis ES products (TsES) [5]. Treatment of J774A.1 or RAW264.7 macrophage cell lines with TsES significantly reduced the expression of LPS-induced pro-inflammatory cytokines, TNF-α, IL-1β, IL-6, and IL-12 but increased the expression of regulatory cytokine; this effect was observed even in the presence of ES products alone [5,6]. Adoptive transfer of macrophages obtained from T. spiralis-infected mice or TsES-treated macrophages into colitis or airway hyperresponsiveness (AHR) mouse models could ameliorate disease severity [7].…”

Section: Introductionmentioning

confidence: 99%

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A novel cystatin derived from Trichinella spiralis suppresses macrophage-mediated inflammatory responses

et al. 2020

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Trichinella spiralis can modulate host immune responses to retain a suitable environment for its long-term survival. Incidentally, the parasite elicits regulatory effects through immunomodulatory molecule release, which can suppress host inflammation and may be used for the treatment of unrelated inflammatory diseases in someday. Here we identified and characterized a novel T. spiralis cystatin (TsCstN), which inhibits inflammation mediated by LPS-treated macrophages.Proteins contained in the excretory-secretory (ES) product of muscle-stage T. spiralis (ES-L1) were fractionated, and each was treated with mouse bone marrow-derived macrophages (mBMDMs) before LPS stimulation. The fractions that exhibited high immunomodulatory property by decreasing pro-inflammatory cytokines or increasing anti-inflammatory cytokines were identified by mass spectrometry. Incidentally, the conserved hypothetical protein (Tsp_04814) was selected for further characterization as it presented the most significant MS score. An annotation of Tsp_04814 using protein structural homology comparison suggested that it has high structural similarity to human cystatin E/M (TM score 0.690). The recombinant T. spiralis novel cystatin (rTsCstN) was expressed in Escherichia coli at a molecular weight of approximately 13 kDa. Mouse anti-rTsCstN polyclonal antibody (pAb) could detect native TsCstN in crude worm antigens (CWA) and ES-L1 and be predominantly localized in the stichosome and subcuticular cells. rTsCstN inhibited cysteine proteases in vitro, especially cathepsin L, at an optimal pH of 6. Besides, rTsCstN could be internalized into mBMDMs, which were mostly distributed in the cytoplasm and lysosome both before and after LPS stimulation. To evaluate the rTsCstN immunomodulatory properties on mBMDMs, rTsCstN was incubated with mBMDM before LPS stimulation; this demonstrated that rTsCstN suppressed pro-inflammatory cytokine production and MHC class II expression.T. spiralis L1-derived TsCstN was characterized as a novel cysteine PLOS NEGLECTED TROPICAL DISEASES

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Section: Discussionmentioning

confidence: 66%

Section: Introductionmentioning

confidence: 99%

A novel cystatin derived from Trichinella spiralis suppresses macrophage-mediated inflammatory responses

et al. 2020

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“…It is necessary to identify the specific molecules in the ES products involved in immunomodulation (46). LC-MS/MS identified more than 280 protein components in T. spiralis AES with 4 proteins having potential regulatory functions that include cysteine protease inhibitor, serine protease, 53 kDa excretory/secretory antigen, and glutathione-S-transferase (47)(48)(49). Some of the proteins secreted by the T. spiralis adult worm have revealed regulatory functions to the host immune system.…”

Section: Discussionmentioning

confidence: 99%

Excretory/Secretory Products From Trichinella spiralis Adult Worms Attenuated DSS-Induced Colitis in Mice by Driving PD-1-Mediated M2 Macrophage Polarization

et al. 2020

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“…Trichinella spiralis ES proteins ameliorate intestinal injury by promoting IRF4 and M2-related metabolic regulation via STAT6-dependent transformation of classically activated M1 macrophages to alternatively activated M2 macrophages. M2 macrophages have anti-inflammatory properties, and, thus, ES products may have potential as an immunotherapeutic against inflammatory disorders by inducing M2 macrophages (Han et al ., 2019; Kang et al ., 2019). The immune response to T. spiralis is a powerful way to reduce inflammation of the host intestine.…”

Section: Contribution Of Immunology To Clearing Host Inflammation In mentioning

confidence: 99%

Trichinella spiralis:inflammation modulator

et al. 2020

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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.

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Immunomodulatory effects of Trichinella spiralis excretory-secretory antigens on macrophages

Cited by 30 publications

References 32 publications

A novel cystatin derived from Trichinella spiralis suppresses macrophage-mediated inflammatory responses

A novel cystatin derived from Trichinella spiralis suppresses macrophage-mediated inflammatory responses

Excretory/Secretory Products From Trichinella spiralis Adult Worms Attenuated DSS-Induced Colitis in Mice by Driving PD-1-Mediated M2 Macrophage Polarization

Trichinella spiralis:inflammation modulator

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