Partial immunity to Schistosoma mansoni, in the rat, can be obtained by injection of a bilharzian antigen together muramyldipeptide (MDP) in a water in oil emulsion. This immunity is the result of both specific and non specific mechanisms.
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Immunobiology
September 2024
National Council for Scientific and Technical Research (CONICET); Center for Advanced Studies in Human Sciences and Health (CAECIHS), Interamerican Open University (UAI), Buenos Aires, Argentina.
Innate immune cells show enhanced responsiveness to secondary challenges after an initial non-related stimulation (Trained Innate Immunity, TII). Acute NOD2 activation by Muramyl-Dipeptide (MDP) promotes TII inducing the secretion of pro-inflammatory mediators, while a sustained MDP-stimulation down-regulates the inflammatory response, restoring tolerance. Here we characterized in-vitro the response of murine macrophages to lipopolysaccharide (LPS) challenge under NOD2-chronic stimulation.
View Article and Find Full Text PDFActa Pharm Sin B
September 2021
Jiangsu Key Laboratory for Functional Substance of Chinese Medicine, Stake Key Laboratory Cultivation Base for TCM Quality and Efficacy, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Aberrant activation of NLRP3 inflammasome in colonic macrophages strongly associates with the occurrence and progression of ulcerative colitis. Although targeting NLRP3 inflammasome has been considered to be a potential therapy, the underlying mechanism through which pathway the intestinal inflammation is modulated remains controversial. By focusing on the flavonoid lonicerin, one of the most abundant constituents existed in a long historical anti-inflammatory and anti-infectious herb Thunb.
View Article and Find Full Text PDFNat Commun
March 2019
Department of Medicine, Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.
During infection, transcription factor interferon regulatory factor 5 (IRF5) is essential for the control of host defense. Here we show that the microtubule-associated guanine nucleotide exchange factor (GEF)-H1, is required for the phosphorylation of IRF5 by microbial muramyl-dipeptides (MDP), the minimal structural motif of peptidoglycan of both Gram-positive and Gram-negative bacteria. Specifically, GEF-H1 functions in a microtubule based recognition system for microbial peptidoglycans that mediates the activation of IKKε which we identify as a new upstream IKKα/β and IRF5 kinase.
View Article and Find Full Text PDFBioconjug Chem
April 2019
Leiden Institute of Chemistry , Leiden University, Einsteinweg 55 , 2333 CC Leiden , The Netherlands.
Simultaneous triggering of Toll-like receptors (TLRs) and NOD-like receptors (NLRs) has previously been shown to synergistically activate monocytes, dendritic cells, and macrophages. We applied these properties in a T-cell vaccine setting by conjugating the NOD2-ligand muramyl-dipeptide (MDP) and TLR2-ligand PamCSK to a synthetic peptide derived from a model antigen. Stimulation of human DCs with the MDP-peptide-PamCSK conjugate led to a strongly increased secretion of pro-inflammatory and Th1-type cytokines and chemokines.
View Article and Find Full Text PDFACS Chem Biol
March 2019
Laboratory of Chemical Biology and Microbial Pathogenesis , The Rockefeller University, New York , New York 10065 , United States.
The peptidoglycan fragments γ-d-glutamyl- meso-diaminopimelic acid (iE-DAP) and muramyl-dipeptide (MDP) are microbial-specific metabolites that activate intracellular pattern recognition receptors and stimulate immune signaling pathways. While extensive structure-activity studies have demonstrated that these bacterial cell wall metabolites trigger NOD1- and NOD2-dependent signaling, their direct binding to these innate immune receptors or other proteins in mammalian cells has not been established. To characterize these fundamental microbial metabolite-host interactions, we synthesized a series of peptidoglycan metabolite photoaffinity reporters and evaluated their cross-linking to NOD1 and NOD2 in mammalian cells.
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