Schistosome-derived omega-1 drives Th2 polarization by suppressing protein synthesis following internalization by the mannose receptor

Everts, Bart; Hussaarts, Leonie; Driessen, Nicole N.; Meevissen, Moniek H.J.; Schramm, Gabriele; Ham, Alwin J. van der; Hoeven, B. van der; Scholzen, Thomas; Burgdorf, Sven; Mohrs, Markus; Pearce, Edward J.; Hokke, Cornelis H.; Haas, Helmut; Smits, Hermelijn H.; Yazdanbakhsh, Maria

doi:10.1084/jem.20111381

Cited by 203 publications

(264 citation statements)

References 63 publications

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“…However, we could not detect expression of SIGNR1 in BMDCs (data not shown), suggesting that there are other receptors that LNFPIII utilizes to interact and enter into APCs to modulate immune functions. These results are similar to those of an earlier study showing that glycans in SEA require at least three C-type lectins, MglI, mannose receptor 1 (MR1), and DC-SIGN, to mature APCs into cells that drive Th2 immune responses (22,56). In mice, the presence of multiple C-type lectin receptors and multiple copies of the SIGNR1, a homologue of human DC-SIGN, makes it difficult to selectively study the role of lectins in LNFPIIImediated alternative activation of APCs.…”

Section: Discussionsupporting

confidence: 90%

“…S2a in the supplemental material). Further support for this observation comes from Everts et al (22), who demonstrated that glycans on the S. mansoni egg protein omega-1 were required for omega-1 binding to and uptake by APCs, confirming the requirement of helminth glycans in initiating APC maturation that leads to CD4 ϩ T cell biasing to Th2 type. However, while Everts et al (22) confirmed the requirement for glycans, they suggested that the glycans on omega-1 were utilized only for omega-1 uptake by dendritic cells and were not directly involved in driving DC maturation toward DC2s.…”

Section: Discussionmentioning

confidence: 81%

“…They suggested that because Lewis x and other glycan structures found on omega-1 were not multivalent, they were unable to drive DCs toward a DC2 phenotype. Everts et al (22) stated that the loss of total ribosomal RNAs in APCs due to omega-1 RNase activity is what primes DCs to induce CD4 ϩ Th2-type maturation. An alternative explanation for omega-1 activity is that the RNase activity kills APCs, releasing danger-associated molecular patterns into the environment, which then activates viable APCs to embark on an alternative maturation process.…”

Section: Discussionmentioning

confidence: 99%

“…ϩ Th2-type responses (22). Lewis x is a glycan expressed on multiple stages of S. mansoni and is present on omega-1, which carries tandem repeats of Lewis x , LacNac(LN), and LacdiNAcLDN motifs (23).…”

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confidence: 99%

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Immunomodulatory Glycan Lacto-N-Fucopentaose III Requires Clathrin-Mediated Endocytosis To Induce Alternative Activation of Antigen-Presenting Cells

et al. 2014

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The mechanism of alternative activation of antigen-presenting cells (APCs) is largely unknown. Lacto-N-fucopentaose III (LNFPIII) is a biologically conserved pentasaccharide that contains the Lewis x trisaccharide. LNFPIII conjugates and schistosome egg antigens, which contain the Lewis x trisaccharide, drive alternative activation of APCs and induce anti-inflammatory responses in vivo, preventing inflammation-based diseases, including psoriasis, transplant organ rejection, and metabolic disease. In this study, we show that LNFPIII conjugates and schistosome egg antigens interact with APCs via a receptor-mediated process, requiring internalization of these molecules through a clathrin/dynamin-dependent but caveolus-independent endocytic pathway. Using inhibitors/small interfering RNA (siRNA) against dynamin and clathrin, we show for the first time that endocytosis of Lewis x -containing glycans is required to drive alternative maturation of antigen-presenting cells and Th2 immune responses. We identified mouse SIGNR-1 as a cell surface receptor for LNFPIII conjugates. Elimination of SIGNR-1 showed no effect on uptake of LNFPIII conjugates, suggesting that other receptors bind to and facilitate uptake of LNFPIII conjugates. We demonstrate that disruption of actin filaments partially prevented the entry of LNFPIII conjugates into APCs and that LNFPIII colocalizes with both early and late endosomal markers and follows the classical endosomal pathway leading to lysosome maturation. The results of this study show that the ability of LNFPIII to induce alternative activation utilizes a receptor-mediated process that requires a dynamin-dependent endocytosis. Thus, key steps have been defined in the previously unknown mechanism of alternative activation that ultimately leads to induction of anti-inflammatory responses.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Immunomodulatory Glycan Lacto-N-Fucopentaose III Requires Clathrin-Mediated Endocytosis To Induce Alternative Activation of Antigen-Presenting Cells

et al. 2014

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“…The skewed response reaches its peak~8 weeks post infection, resulting in acute symptoms in patients. 4,5 Then, the Th2 response is downregulated and the newly formed granulomas shrink during the chronic stage at week 12. 6 Thus, the Th2 response promotes gene transcription pathways associated with granuloma formation and collagen synthesis.…”

Section: Introductionmentioning

confidence: 99%

Toxoplasma gondii GRA15II effector-induced M1 cells ameliorate liver fibrosis in mice infected with Schistosomiasis japonica

et al. 2016

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Recent studies indicated that type II Toxoplasma gondii (Tg) GRA15 II favored the generation of classically activated macrophages (M1), whereas type I/III TgROP16 I/III promoted the polarization of alternatively activated macrophages (M2). A number of studies have demonstrated that M2 cells are involved in the pathogenesis of the liver fibrogenesis caused by Schistosoma japonicum. The purpose of the present study was to explore the inhibitory effect of Toxoplasma-derived TgGRA15 II on mouse hepatic fibrosis with schistosomiasis. The gra15 II and rop16 I/III genes were amplified from strains T. gondii PRU and Chinese 1 Wh3, respectively. Lentiviral vectors containing the gra15 II or rop16 I/III plasmid were constructed and used to infect the RAW264.7 cell line. The polarization of the transfected cells was evaluated, followed by co-culture of the biased macrophages with mouse hepatic stellate JS1 cells. Then, mice were injected with GRA15 II -driven macrophages via the tail vein and infected with S. japonicum cercariae. TgGRA15 II induced a M1-biased response, whereas TgROP16 I/III drove the macrophages to a M2-like phenotype. The in vitro experiments indicated that JS1 cell proliferation and collagen synthesis were decreased following co-culture with TgGRA15 II -activated macrophages. Furthermore, mice inoculated with TgGRA15 II -biased macrophages displayed a notable alleviation of collagen deposition and granuloma formation in their liver tissues. Our results suggest that TgGRA15 II -induced M1 cells may dampen the M2 dominant pathogenesis of hepatic fibrosis and granulomatosis. These results provide insights into the use of parasite-derived immunomodulators as potential anti-fibrosis agents and to re-balance the schistosomiasis-induced immune response.

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Immobilized peptide‐N‐glycosidase F onto magnetic nanoparticles: A biotechnological tool for protein deglycosylation under native conditions

Bidondo

Festari²,

Freire³

et al. 2021

Biotech and App Biochem

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The elucidation of glycans biological function is essential to understand their role in biological processes, both normal and pathological. Immobilized glycoenzymes are excellent tools for this purpose as they can selectively release glycans from glycoproteins without altering their backbone. They can be easily removed from the reaction mixture avoiding their interference in subsequent experiments. Here, we describe the immobilization of peptide-N-glycosidase F (PNGase F) onto silica magnetic nanoparticles with immobilization yields of 86% and activity yields of 12%. Immobilized PNGase F showed higher thermal stability than its soluble counterpart, and could be reused for at least seven deglycosylation cycles. It was efficient in the deglycosylation of several glycoproteins (ribonuclease B, bovine fetuin, and ovalbumin) and a protein lysate from the parasite Fasciola hepatica under native conditions, with similar performance to that of the soluble enzyme. Successful deglycosylation was evidenced by a decrease in specific lectin recognition of the glycoproteins (40%-80%). Moreover, deglycosylated F. hepatica lysate allowed us to confirm the role of parasite N-glycans in the inhibition of the lipopolysaccharide-induced maturation of dendritic cells. Immobilized PNGase F probed to be a robust biotechnological tool for deglycosylation of glycoproteins and complex biological samples under native conditions.

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Schistosome-derived omega-1 drives Th2 polarization by suppressing protein synthesis following internalization by the mannose receptor

Abstract: Schistosome ribonuclease Omega-1 primes DCs to generate Th2 responses by binding and internalization by the mannose receptor and by subsequently impairing protein synthesis.

Cited by 203 publications

References 63 publications

Immunomodulatory Glycan Lacto-N-Fucopentaose III Requires Clathrin-Mediated Endocytosis To Induce Alternative Activation of Antigen-Presenting Cells

Immunomodulatory Glycan Lacto-N-Fucopentaose III Requires Clathrin-Mediated Endocytosis To Induce Alternative Activation of Antigen-Presenting Cells

Toxoplasma gondii GRA15II effector-induced M1 cells ameliorate liver fibrosis in mice infected with Schistosomiasis japonica

Immobilized peptide‐N‐glycosidase F onto magnetic nanoparticles: A biotechnological tool for protein deglycosylation under native conditions

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