ArticlePloS one2015
A Neoglycoconjugate Containing the Human Milk Sugar LNFPIII Drives Anti-Inflammatory Activation of Antigen Presenting Cells in a CD14 Dependent Pathway.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 31 citations in OpenAlex.
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- Preoperative hypoalbuminemia and surgical complications in benign minimally invasive hysterectomy.Surgical endoscopy · 2026Article
- The Impact of Helminths on Colorectal Cancer: From Infections to the Isolation of Biotherapeutics.Pathogens (Basel, Switzerland) · 2025Review
- The Human Milk Oligosaccharide Lacto-N-Fucopentaose III Conjugated to Dextran Inhibits HIV Replication in Primary Human Macrophages.Nutrients · 2025Article
- Novel Dairy Fermentates Have Differential Effects on Key Immune Responses Associated with Viral Immunity and Inflammation in Dendritic Cells.Foods (Basel, Switzerland) · 2024Article
- Estrogen-sensitive activation of SGK1 induces M2 macrophages with anti-inflammatory properties and a Th2 response at the maternal-fetal interface.Reproductive biology and endocrinology : RB&E · 2023Article
- Pathophysiological basis and promise of experimental therapies for Gulf War Illness, a chronic neuropsychiatric syndrome in veterans.Psychopharmacology · 2023Review
- Evaluation of delayed LNFPIII treatment initiation protocol on improving long-term behavioral and neuroinflammatory pathology in a mouse model of Gulf War Illness.Brain, behavior, & immunity - health · 2022Article
- Schistosome immunomodulators.PLoS pathogens · 2021Review
- Acceptive Immunity: The Role of Fucosylated Glycans in Human Host-Microbiome Interactions.International journal of molecular sciences · 2021Review
- Gulf War Illness: Mechanisms Underlying Brain Dysfunction and Promising Therapeutic Strategies.Pharmacology & therapeutics · 2021Review
- A Comparison of Two Structurally Related Human Milk Oligosaccharide Conjugates in a Model of Diet-Induced Obesity.Frontiers in immunology · 2021Article
- Helminth Glycans at the Host-Parasite Interface and Their Potential for Developing Novel Therapeutics.Frontiers in molecular biosciences · 2021Review
- Assessing the Beneficial Effects of the Immunomodulatory Glycan LNFPIII on Gut Microbiota and Health in a Mouse Model of Gulf War Illness.International journal of environmental research and public health · 2020Article
- The Potential Role of Schistosome-Associated Factors as Therapeutic Modulators of the Immune System.Infection and immunity · 2020Review
- Neurochemical and neuroinflammatory perturbations in two Gulf War Illness models: Modulation by the immunotherapeutic LNFPIII.Neurotoxicology · 2020Article
- Tumor progression locus 2 (TPL2) in tumor-promoting Inflammation, Tumorigenesis and Tumor Immunity.Theranostics · 2020Review
- The ectodomains of the lymphocyte scavenger receptors CD5 and CD6 interact with tegumental antigens from Echinococcus granulosus sensu lato and protect mice against secondary cystic echinococcosis.PLoS neglected tropical diseases · 2018Article
- Structural Characterization of Biofunctionalized Gold Nanoparticles by Ultrahigh-Resolution Mass Spectrometry.ACS nano · 2017Article
- Toll-Like Receptor 4, but Not Neutrophil Extracellular Traps, Promote IFN Type I Expression to Enhance Th2 Responses toFrontiers in immunology · 2017Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
The milk pentasaccharide LNFPIII has therapeutic action for metabolic and autoimmune diseases and prolongs transplant survival in mice when presented as a neoglycoconjugate. Within LNFPIII is the Lewisx trisaccharide, expressed by many helminth parasites. In humans, LNFPIII is found in human milk and also known as stage-specific embryonic antigen-1. LNFPIII-NGC drives alternative activation of macrophages and dendritic cells via NFκB activation in a TLR4 dependent mechanism. However, the connection between LNFPIII-NGC activation of APCs, TLR4 signaling and subsequent MAP kinase signaling leading to anti-inflammatory activation of APCs remains unknown. In this study we determined that the innate receptor CD14 was essential for LNFPIII-NGC induction of both ERK and NFkB activation in APCs. Induction of ERK activation by LNFPIII-NGC was completely dependent on CD14/TLR4-Ras-Raf1/TPL2-MEK axis in bone marrow derived dendritic cells (BMDCs). In addition, LNFPIII-NGC preferentially induced the production of Th2 "favoring" chemokines CCL22 and matrix metalloprotease protein-9 in a CD14 dependent manner in BMDCs. In contrast, LNFPIII-NGC induces significantly lower levels of Th1 "favoring" chemokines, MIP1α, MIP1β and MIP-2 compared to levels in LPS stimulated cells. Interestingly, NGC of the identical human milk sugar LNnT, minus the alpha 1-3 linked fucose, failed to activate APCs via TLR4/MD2/CD14 receptor complex, suggesting that the alpha 1-3 linked fucose in LNFPIII and not on LNnT, is required for this process. Using specific chemical inhibitors of the MAPK pathway, we found that LNFPIII-NGC induction of CCL22, MMP9 and IL-10 production was dependent on ERK activation. Over all, this study suggests that LNFPIII-NGC utilizes CD14/TLR4-MAPK (ERK) axis in modulating APC activation to produce anti-inflammatory chemokines and cytokines in a manner distinct from that seen for the pro-inflammatory PAMP LPS. These pathways may explain the in vivo therapeutic effect of LNFPIII-NGC treatment for inflammation based diseases.
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