Schistosoma mansoni triggers Dectin-2, which activates the Nlrp3 inflammasome and alters adaptive immune responses
Open accessAbstract
The propensity of helminths, such as schistosomes, to immunomodulate the host's immune system is an essential aspect of their survival. Previous research has demonstrated how soluble schistosomal egg antigens (SEA) dampen TLR-signaling during innate immune responses. We show here that the suppressive effect by SEA on TLR signaling is simultaneously coupled to the activation of the Nlrp3 (NLR family, pyrin domain containing 3) inflammasome and thus IL-1β production. Therefore, the responsible protein component of SEA contains the second signal that is required to trigger proteolytic pro-IL-1β processing. Moreover, the SEA component binds to the Dectin-2/FcRγ (Fc receptor γ chain) complex and activates the Syk kinase signaling pathway to induce reactive oxygen species and potassium efflux. As IL-1β has been shown to be an essential orchestrator against several pathogens we studied the in vivo consequences of Schistosoma mansoni infection in mice deficient in the central inflammasome adapter ASC and Nlrp3 molecule. These mice failed to induce local IL-1β levels in the liver and showed decreased immunopathology. Interestingly, antigen-specific Th1, Th2, and Th17 responses were down-regulated. Overall, these data imply that component(s) within SEA induce IL-1β production and unravel a crucial role of Nlrp3 during S. mansoni infection.
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Schistosome glycans bind to Dectin-1 and Dectin-2 and prime DCs for enhanced Th2 cell development via autocrine prostaglandin-E2 (PGE2) and OX40L.
“schistosome glycans bind to the C-type lectin receptors Dectin-1 and Dectin-2 (Ritter et al., 2010) and prime DCs for enhanced Th2 cell development via autocrine prostaglandin-E2 (PGE2) and OX40L”
From Modulation of Host Immunity by Helminths: The Expanding Repertoire of Parasite Effector Molecules (2018) · cites this paper as Ritter et al., 2010
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- Authors
- Ritter, M., Gross, O., Kays, S., Ruland, J., Nimmerjahn, F., Saijo, S., Tschopp, J., Layland, L. E., & Prazeres da Costa, C.
- Affiliations
- Technical University of Munich (DE)
- University of Lausanne (CH)
- TUM Klinikum (DE)
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- Institute of Medical Science, The University of Tokyo (JP)
- University Hospital Bonn (DE)
- Institute for Microbiology, Immunology and Hygiene, Technische Universität München, 81675 Munich, Germany;
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2010-11-08
- Volume
- 107
- Issue
- 47
- Pages
- 20459-20464
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2996650
- OpenAlex
- W2129113472
- Cited by
- 243
- References
- 38
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 11 · 2023: 7 · 2022: 13 · 2021: 11 · 2020: 20 · 2019: 12 · 2018: 22 · 2017: 14 · 2016: 29 · 2015: 16 · 2014: 15 · 2013: 22 · 2012: 22
- FWCI
- 7.95
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- IRIS (submittedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- Site cant be reached (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Life Sciences › Immunology and Microbiology › Parasitology › Parasites and Host Interactions
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- Schistosoma mansoni, Dectin-2, NLRP3 inflammasome, soluble egg antigen, IL-1β, helminth immunomodulation, Syk signaling, reactive oxygen species, potassium efflux, ASC, Th1/Th2/Th17 responses, innate immunity
- MeSH terms
- NLR Family, Pyrin Domain-Containing 3 Protein, Analysis of Variance, Animals, Antigens, Helminth, Carrier Proteins, Dendritic Cells, Gene Expression Regulation, Mice, Inbred C57BL, Schistosomiasis, Specific Pathogen-Free Organisms, Blotting, Western, Mice, Knockout, Lectins, C-Type, Toll-Like Receptors, Mice, Interleukin-1beta, Adaptive Immunity, Inflammasomes
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