Plasmacytoid dendritic cells mediate anti-inflammatory responses to a gut commensal molecule via both innate and adaptive mechanisms
Open accessAbstract
Polysaccharide A (PSA), the archetypical immunomodulatory molecule of the gut commensal Bacteroides fragilis, induces regulatory T cells to secrete the anti-inflammatory cytokine interleukin-10 (IL-10). The cellular mediators of PSA's immunomodulatory properties are incompletely understood. In a mouse model of colitis, we find that PSA requires both innate and adaptive immune mechanisms to generate protection. Plasmacytoid DCs (PDCs) exposed to PSA do not produce proinflammatory cytokines, but instead they specifically stimulate IL-10 secretion by CD4+ T cells and efficiently mediate PSA-afforded immunoprotection. PSA induces and preferentially ligates Toll-like receptor 2 on PDCs but not on conventional DCs. Compared with other TLR2 ligands, PSA is better at enhancing PDC expression of costimulatory molecules required for protection against colitis. PDCs can thus orchestrate the beneficial immunoregulatory interaction of commensal microbial molecules, such as PSA, through both innate and adaptive immune mechanisms.
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PSA induces IL-10 secretion by CD4+ T cells and promotes differentiation of naive CD4+ T cells into TH1 over TH2 cells.
“PSA induces secretion of the potent anti-inflammatory cytokine IL-10 by CD4+ T cells and promotes the differentiation of naive CD4+ T cells into TH1 cells over TH2 cells.”
From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as Dasgupta et al., 2014
IL-10 production is primarily mediated by dendritic cells, which internalize PSA and present fragments to CD4+ T cells with MHC-II, stimulating activation and clonal expansion.
“The production of IL-10 is primarily mediated by DCs, which internalize PSA and present fragments to CD4+ T cells in conjunction with the major histocompatibility complex class II (MHC-II), thus stimulating activation and clonal expansion of T cells.”
From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as Dasgupta et al., 2014
PSA-induced IL-10 inhibits mucosal effector T cells, particularly TH17 cells, and protects mice in experimental colitis models.
“The PSA-induced production of IL-10 inhibits the activity of mucosal effector T cells, in particular of TH17 cells, and thereby protects mice in experimental models of colitis (Dasgupta et al., 2014; Mazmanian et al., 2008).”
From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as Dasgupta et al., 2014
PSA activates TLR2 on dendritic cells, triggering release of cytokines that promote IL-10 production by T cells.
“Importantly, PSA also activates toll-like receptor (TLR) 2 expressed on the surface of DCs, which triggers the release of cytokines that promote IL-10 production by T cells (Cobb et al., 2004; Dasgupta et al., 2014; Johnson et al., 2015; Mazmanian et al., 2005; 2008; Telesford et al., 2015; Q. Wang et al., 2006).”
From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as Dasgupta et al., 2014
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References 49 · Cited by 292
Research works printed but not linked: 1
- Smith PM Howitt MR Panikov N Michaud M Gallini CA Bohlooly YM Glickman JN Garrett WS The Microbial Metabolites, Short-Chain Fatty Acids, Regulate Colonic Treg Cell Homeostasis Science 2013 PMC3807819 23828891
- Authors
- Dasgupta, S., Erturk-Hasdemir, D., Ochoa-Reparaz, J., Reinecker, H.-C., & Kasper, D. L.
- Affiliations
- Harvard University (US)
- Massachusetts General Hospital (US)
- Corresponding author
- Kasper, Dennis L.
- Venue
- Cell Host & Microbe
- Publisher
- Elsevier BV
- Published
- 2014-04
- Volume
- 15
- Issue
- 4
- Pages
- 413-423
- ISSN
- 1931-3128 (ISSN-L)
- PMC
- PMC4020153
- OpenAlex
- W2084891825
- Cited by
- 292
- References
- 49
- Citations by year
- 2026: 10 · 2025: 21 · 2024: 25 · 2023: 21 · 2022: 20 · 2021: 32 · 2020: 27 · 2019: 42 · 2018: 29 · 2017: 17 · 2016: 21 · 2015: 18 · 2014: 9
- FWCI
- 9.89
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Host & Microbe (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Crohn's and Colitis Foundation of America
- Crohn's and Colitis Foundation
- National Institute of Allergy and Infectious Diseases (AI1090102, R21AI090102)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK068181, P30DK043351)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- plasmacytoid dendritic cells, polysaccharide A, Bacteroides fragilis, gut commensals, IL-10, regulatory T cells, colitis, TLR2, costimulatory molecules, immunomodulation, innate and adaptive immunity, anti-inflammatory response
- MeSH terms
- Animals, Bacteroides fragilis, Bone Marrow Cells, Cells, Cultured, Dendritic Cells, Encephalomyelitis, Autoimmune, Experimental, Female, Immunity, Innate, Inflammation, Lymphocyte Depletion, Mice, Inbred C57BL, Polysaccharides, Bacterial, CD4-Positive T-Lymphocytes, Interleukin-10, CD28 Antigens, B7-1 Antigen, Mice, Knockout, Adoptive Transfer, Models, Animal, Gastrointestinal Tract, Toll-Like Receptor 2, Mice, B7-2 Antigen, Adaptive Immunity, Inducible T-Cell Co-Stimulator Ligand
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