The Mannose Receptor in Regulation of Helminth-Mediated Host Immunity

Infection with parasitic helminths affects humanity and animal welfare. Parasitic helminths have the capacity to modulate host immune responses to promote their survival in infected hosts, often for a long time leading to chronic infections. In contrast to many infectious microbes, however, the helminths are able to induce immune responses that show positive bystander effects such as the protection to several immune disorders, including multiple sclerosis, inflammatory bowel disease, and allergies. They generally promote the generation of a tolerogenic immune microenvironment including the induction of type 2 (Th2) responses and a sub-population of alternatively activated macrophages. It is proposed that this anti-inflammatory response enables helminths to survive in their hosts and protects the host from excessive pathology arising from infection with these large pathogens. In any case, there is an urgent need to enhance understanding of how helminths beneficially modulate inflammatory reactions, to identify the molecules involved and to promote approaches to exploit this knowledge for future therapeutic interventions. Evidence is increasing that C-type lectins play an important role in driving helminth-mediated immune responses. C-type lectins belong to a large family of calcium-dependent receptors with broad glycan specificity. They are abundantly present on immune cells, such as dendritic cells and macrophages, which are essential in shaping host immune responses. Here, we will focus on the role of the C-type lectin macrophage mannose receptor (MR) in helminth–host interactions, which is a critically understudied area in the field of helminth immunobiology. We give an overview of the structural aspects of the MR including its glycan specificity, and the functional implications of the MR in helminth–host interactions focusing on a few selected helminth species

The acceptor substrate specificity of human β4-galactosyltransferase V indicates its potential function in O-glycosylation

AbstractIn order to assess the function of the different human UDP-Gal:GlcNAc β4-galactosyltransferases, the cDNAs of two of them, β4-GalT I and β4-GalT V, were expressed in the baculovirus/insect cell expression system. The soluble recombinant enzymes produced were purified from the medium and used to determine their in vitro substrate specificities. The specific activity of the recombinant β4-GalT V was more than 15 times lower than that of β4-GalT I, using GlcNAcβ-S-pNP as an acceptor. Whereas β4-GalT I efficiently acts on all substrates having a terminal β-linked GlcNAc, β4-GalT V appeared to be far more restricted in acceptor usage. β4-GalT V acts with high preference on acceptors that contain the GlcNAcβ1→6GalNAc structural element, as found in O-linked core 2-, 4- and 6-based glycans, but not on substrates related to N-linked or blood group I-active oligosaccharides. These results suggest that β4-GalT V may function in the synthesis of lacNAc units on O-linked chains, particularly in tissues which do not express β4-GalT I, such as brain

Демократия «по-украински»

Сегодня наиболее развитые государства западного мира связывают все успехи в социально-экономическом и политическом развитии именно с демократическими формами управления обществом.Сьогодні найбільш розвинені держави західного світу зв'язують всі успіхи в соціально-економічному і політичному розвитку саме з демократичними формами управління суспільством.Отрывок из книги «Украинская национальная идея и украинский национализм»

DC-SIGN mediates binding of dendritic cells to authentic pseudo-LewisY glycolipids of Schistosoma mansoni cercariae, the first parasite-specific ligand of DC-SIGN

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Ascaris Suum Infection Downregulates Inflammatory Pathways in the Pig Intestine In Vivo and in Human Dendritic Cells In Vitro.

Ascaris suum is a helminth parasite of pigs closely related to its human counterpart, A. lumbricoides, which infects almost 1 billion people. Ascaris is thought to modulate host immune and inflammatory responses, which may drive immune hyporesponsiveness during chronic infections. Using transcriptomic analysis, we show here that pigs with a chronic A. suum infection have a substantial suppression of inflammatory pathways in the intestinal mucosa, with a broad downregulation of genes encoding cytokines and antigen-processing and costimulatory molecules. A. suum body fluid (ABF) suppressed similar transcriptional pathways in human dendritic cells (DCs) in vitro. DCs exposed to ABF secreted minimal amounts of cytokines and had impaired production of cyclooxygengase-2, altered glucose metabolism, and reduced capacity to induce interferon-gamma production in T cells. Our in vivo and in vitro data provide an insight into mucosal immune modulation during Ascaris infection, and show that A. suum profoundly suppresses immune and inflammatory pathways

Nucleotide sequence of the gene encoding the F72 fimbrial subunit of a uropathogenic Escherichia coli strain

The cloned DNA fragment encoding the F72 fimbrial subunit from the uropathogenic Escherichia coli strain AD110 has been identified. The nucleotide sequence of the structural gene and of 196 bp of the noncoding region preceding the gene was determined. The structural gene codes for a polypeptide of 188 amino acid residues, including a 21-residue N-terminal signal sequence. The nucleotide sequence and the deduced amino acid sequence of the F72 gene were compared with the reported sequences of the papA gene (Båga et al., 1984). Both genes code for subunits of fimbriae that are involved in mannose-resistant hemagglutination (MRHA) of human erythrocytes. The available data show that there is absolute homology between the noncoding regions preceding both genes over 129 bp. The two proteins are homologous at the N terminus and C terminus; there is less, but significant, homology in the region between the N and C termini

Analysis of the primary structure of P-fimbrillins of uropathogenic Escherichia coli

The ability of uropathogenic Escherichia coli to adhere to uroepithelial cells is a prerequisite for successful colonization of the urinary tract by this organism, and the subsequent development of urinary tract infections. The mechanism of adherence has been studied intensively during the last years . Many investigators support the view that P-fimbriae play an important role in this adhesion process. P-fimbriae recognize a disaccharide with the structure α-D-Galp β-D-Galp in the uroepithelium. This structure is also part of the P-bloodgroup antigen . Adherence of p-fimbriated cells to the P blood group antigen on the surface of human erytrocytes causes mannose resistant hemagglutination (MRHA)