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Angela Berzi, Stefania Ordanini, Ben Joosten, Daria Trabattoni, Alessandra Cambi, Anna Bernardi, Mario Clerici
DC-SIGN, a C-type lectin mainly expressed by DCs, mediates antigen uptake and can induce specific immune responses, depending on the ligand involved. Owing to these properties, DC-SIGN is an attracting target for approaches aimed at tailoring the immune response towards specific immunologic outcomes. A multivalent DC-SIGN ligand (Polyman26), containing at its core a fluorescent "rod-like" spacer and able to inhibit DC-SIGN mediated HIV infection in nanomolar concentration, has been recently developed by our group...
October 13, 2016: Scientific Reports
Toshi Horie, Megumi Inomata, Takeshi Into, Yoshiaki Hasegawa, Noriyuki Kitai, Fuminobu Yoshimura, Yukitaka Murakami
Bacterial glycoproteins are associated with physiological and pathogenic functions of bacteria. It remains unclear whether bacterial glycoproteins can bind to specific classes of lectins expressed on host cells. Tannerella forsythia is a gram-negative oral anaerobe that contributes to the development of periodontitis. In this study, we aimed to find lectin-binding glycoproteins in T. forsythia. We performed affinity chromatography of wheat germ agglutinin, which binds to N-acetylglucosamine (GlcNAc) and sialic acid (Sia), and identified OmpA-like protein as the glycoprotein that has the highest affinity...
2016: PloS One
Benedetta Bertolotti, Beáta Oroszová, Ieva Sutkeviciute, Ladislav Kniežo, Franck Fieschi, Kamil Parkan, Zuzana Lovyová, Martina Kašáková, Jitka Moravcová
The discovery of effective ligands for DC-SIGN receptor is one of the most challenging concepts of antiviral drug design due to the importance of this C-type lectin in infection processes. DC-SIGN recognizes mannosylated and fucosylated oligosaccharides but glycosidic linkages are accessible to both chemical and enzymatic degradations. To avoid this problem, the synthesis of stable glycoside mimetics has attracted increasing attention. In this work we establish for the first time mono- and divalent C-glycosides based on d-manno and l-fuco configurations as prospective DC-SIGN ligands...
September 9, 2016: Carbohydrate Research
Sukriti Sukriti, Nirupma Trehanpati, Manoj Kumar, Chandana Pande, Syed S Hissar, Shiv Kumar Sarin
BACKGROUND: Dendritic cells (DCs) promote pathogen recognition, uptake and presentation of antigen through DC-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN) and toll-like receptors (TLRs). AIMS AND OBJECTIVES: We aimed to study temporal changes in DCs, TLRs and DC-SIGN during acute viral hepatitis B (AVHB) infection and compare them to chronic (CHB) and to investigate the earliest time point of activated pathogen recognition receptors in hepatitis B viral infection...
September 22, 2016: Hepatology International
Pablo E Piñeyro, Sakthivel Subramaniam, Scott P Kenney, C Lynn Heffron, Luis G Giménez-Lirola, Xiang-Jin Meng
Porcine reproductive and respiratory syndrome virus (PRRSV) is an economically important global swine pathogen. PRRSV infects porcine dendritic cells (DCs), but the effects of the interactions with DCs are largely unknown. Current research focuses on the production and regulation of interferons and selected inflammatory cytokines in DCs, which may play key roles in immune modulation. In addition, PRRSV also downregulates swine leukocyte antigen class I (SLA-I), SLA-II, and CD80/86 costimulatory molecules in DCs...
September 19, 2016: Viral Immunology
Nicolò Mauro, Paolo Ferruti, Elisabetta Ranucci, Amedea Manfredi, Angela Berzi, Mario Clerici, Valeria Cagno, David Lembo, Alessandro Palmioli, Sara Sattin
The initial steps of viral infections are mediated by interactions between viral proteins and cellular receptors. Blocking the latter with high-affinity ligands may inhibit infection. DC-SIGN, a C-type lectin receptor expressed by immature dendritic cells and macrophages, mediates human immunodeficiency virus (HIV) infection by recognizing mannose clusters on the HIV-1 gp120 envelope glycoprotein. Mannosylated glycodendrimers act as HIV entry inhibitors thanks to their ability to block this receptor. Previously, an amphoteric, but prevailingly cationic polyamidoamine named AGMA1 proved effective as infection inhibitor for several heparan sulfate proteoglycan-dependent viruses, such as human papilloma virus HPV-16 and herpes simplex virus HSV-2...
2016: Scientific Reports
Bojana Milutinovic, Ninoslav Mitic, Jelena Roncevic, Sanja Goc, Miroslava Jankovic
This study was aimed at evaluation of the contribution of acid-soluble glycoproteins (ASG)/mucins and extracellular vesicles (EVs), yet unexplored components of human seminal plasma (hSP) to the complexity of its glycome. Gaining insight into the native presentation and distribution of glycans across hSP could help establish molecular environments supporting specific biological activities based on unique ligand capacities. Soluble and particulate fractions of hSP from healthy subjects were analyzed by gel filtration, electrophoresis, ion-exchange chromatography and a solid phase assay with immobilized charge-resolved glycospecies to test their reactivity with plant lectins, carbohydrate-binding antibodies and selected human lectins...
November 1, 2016: Archives of Biochemistry and Biophysics
Yi-Wen Qian, Chuan Li, Ai-Ping Jiang, Shengfang Ge, Ping Gu, Xianqun Fan, Tai-Sheng Li, Xia Jin, Jian-Hua Wang, Zhi-Liang Wang
Approximately 70% of HIV-1 infected patients acquire ocular opportunistic infections and manifest eye disorders during the course of their illness. The mechanisms by which pathogens invade the ocular site, however, are unclear. Under normal circumstance, vascular endothelium and retinal pigment epithelium (RPE) that possess a well-developed tight junction complex form the blood-retinal barrier (BRB) to prevent pathogen invasion. We hypothesize that the disruption of BRB allows pathogen entry into the ocular sites...
September 7, 2016: Journal of Biological Chemistry
Joanna Mikulak, Ferdinando Oriolo, Federica Portale, Paolo Tentorio, Xiqian Lan, Moin A Saleem, Karl Skorecki, Pravin C Singhal, Domenico Mavilio
BACKGROUND: Patients of African ancestry with untreated HIV-1 infection and carrying the G1 or G2 kidney disease risk variants (Vs) at the APOL1 gene have a tenfold higher risk of developing HIV-associated nephropathy (HIVAN) compared to those with the non-risk wild type (WT) G0 variant. However, the mechanistic contribution of the APOL1 allelic state to kidney injury in HIV-1 infection remains to be elucidated. RESULTS: Non-risk WT APOL1 is associated with lower intracellular levels of HIV-1 in conditionally immortalized human podocytes, while the over expression of G1 or G2 risk Vs significantly increases viral accumulation...
2016: Retrovirology
M Rodriguez-Garcia, Z Shen, F D Barr, A W Boesch, M E Ackerman, J C Kappes, C Ochsenbauer, C R Wira
Dendritic cells (DCs) throughout the female reproductive tract (FRT) were examined for phenotype, HIV capture ability and innate anti-HIV responses. Two main CD11c(+) DC subsets were identified: CD11b(+) and CD11b(low) DCs. CD11b(+)CD14(+) DCs were the most abundant throughout the tract. A majority of CD11c(+)CD14(+) cells corresponded to CD1c(+) myeloid DCs, whereas the rest lacked CD1c and CD163 expression (macrophage marker) and may represent monocyte-derived cells. In addition, we identified CD103(+) DCs, located exclusively in the endometrium, whereas DC-SIGN(+) DCs were broadly distributed throughout the FRT...
August 31, 2016: Mucosal Immunology
Yuan Guo, Chadamas Sakonsinsiri, Inga Nehlmeier, Martin A Fascione, Haiyan Zhang, Weili Wang, Stefan Pöhlmann, W Bruce Turnbull, Dejian Zhou
A highly efficient cap-exchange approach for preparing compact, dense polyvalent mannose-capped quantum dots (QDs) has been developed. The resulting QDs have been successfully used to probe multivalent interactions of HIV/Ebola receptors DC-SIGN and DC-SIGNR (collectively termed as DC-SIGN/R) using a sensitive, ratiometric Förster resonance energy transfer (FRET) assay. The QD probes specifically bind DC-SIGN, but not its closely related receptor DC-SIGNR, which is further confirmed by its specific blocking of DC-SIGN engagement with the Ebola virus glycoprotein...
April 4, 2016: Angewandte Chemie
Otavio Cabral-Marques, Rodrigo Nalio Ramos, Lena F Schimke, Taj Ali Khan, Eduardo Pinheiro Amaral, Caio César Barbosa Bomfim, Osvaldo Reis Junior, Tabata Takahashi França, Christina Arslanian, Joanna Darck Carola Correia Lima, Cristina Worm Weber, Janaíra Fernandes Ferreira, Fabiola Scancetti Tavares, Jing Sun, Maria Regina D Imperio Lima, Marília Seelaender, Vera Lucia Garcia Calich, José Alexandre Marzagão Barbuto, Beatriz Tavares Costa-Carvalho, Gabriela Riemekasten, Gisela Seminario, Liliana Bezrodnik, Luigi Notarangelo, Troy R Torgerson, Hans D Ochs, Antonio Condino-Neto
BACKGROUND: CD40 ligand (CD40L) deficiency predisposes to opportunistic infections, including those caused by fungi and intracellular bacteria. Studies of CD40L-deficient patients reveal the critical role of CD40L-CD40 interaction for the function of T-, B-, and dendritic cells. However, the consequences of CD40L deficiency on macrophage function remain to be investigated. OBJECTIVES: To determine the impact of CD40L absence on monocytes-derived macrophage (MDMs) responses...
August 20, 2016: Journal of Allergy and Clinical Immunology
Y Zhang, Y Luo, W Li, J Liu, M Chen, H Gu, B Wang, X Yao
BACKGROUND: Atopic dermatitis (AD) is a common inflammatory skin disease, concomitant with allergic reactions to allergens. However, the exact mechanisms of allergen-induced immune responses in AD are not clear. The aim of this study is to explore the role of DC-SIGN in capturing and processing glycan-containing allergens and in the subsequent DC activation and T helper cell polarization in AD patients. METHODS: DC-SIGN expression on DCs from AD patients was analysed by confocal microscopy and flow cytometry...
August 9, 2016: Journal of Dermatological Science
Daniel Sepúlveda-Crespo, Rafael Ceña-Díez, José Luis Jiménez, Ma Ángeles Muñoz-Fernández
This review provides an overview of the development of different dendrimers, mainly polyanionic, against human immunodeficiency virus (HIV) and genital herpes (HSV-2) as topical microbicides targeting the viral entry process. Vaginal topical microbicides to prevent sexually transmitted infections such as HIV and HSV-2 are urgently needed. To inhibit HIV/HSV-2 entry processes, new preventive targets have been established to maximize the current therapies against wild-type and drug-resistant viruses. The entry of HIV/HSV-2 into target cells is a multistep process that triggers a cascade of molecular interactions between viral envelope proteins and cell surface receptors...
August 12, 2016: Medicinal Research Reviews
S Al-Hajj, A Heraud, C Lefort, L Lamendour, I Kazma, P Gatault, M Buchler, C Baron, J-M- Halimi
OBJECTIVE: Excessive salt intake may result in the development of hypertension. Recent studies indicated that high sodium concentrations polarize the T-cell immune response toward TH17. Moreover, high salt diet increases interstitial sodium concentration (up to 180 mol/L) and skin macrophage and dendritic cell (DC) density. Furthermore, hypertension was shown to be transferable from hypertensive to normotensive animals through infusion of DC from hypertensive animals. However, the effects of high sodium concentration on DC function remain unknown...
September 2016: Journal of Hypertension
Chiraz Hamimi, Annie David, Pierre Versmisse, Laurence Weiss, Timothée Bruel, David Zucman, Victor Appay, Arnaud Moris, Marie-Noëlle Ungeheuer, Caroline Lascoux-Combe, Françoise Barré-Sinoussi, Michaela Muller-Trutwin, Faroudy Boufassa, Olivier Lambotte, Gianfranco Pancino, Asier Sáez-Cirión
HIV controllers (HICs), rare HIV-1 infected individuals able to control viral replication without antiretroviral therapy, are characterized by an efficient polyfunctional and cytolytic HIV-specific CD8+ T cell response. The mechanisms underlying the induction and maintenance of such response in many HICs despite controlled viremia are not clear. Dendritic cells play a crucial role in the generation and reactivation of T cell responses but scarce information is available on those cells in HICs. We found that monocyte derived dendritic cells (MDDCs) from HICs are less permissive to HIV-1 infection than cells from healthy donors...
2016: PloS One
Mariano Prado Acosta, Sandra M Ruzal, Sandra M Cordo
Many species of Lactobacillus sp. possess Surface(s) layer proteins in their envelope. Among other important characteristics S-layer from Lactobacillus acidophilus binds to the cellular receptor DC-SIGN (Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin; CD209), which is involved in adhesion and infection of several families of bacteria. In this report we investigate the activity of new S-layer proteins from the Lactobacillus family (Lactobacillus acidophilus, Lactobacillus brevis, Lactobacillus helveticus and Lactobacillus kefiri) over the infection of representative microorganisms important to human health...
November 2016: International Journal of Biological Macromolecules
Marisa Cruz-Aguilar, Antonia I Castillo-Rodal, Alejandro Schcolnik-Cabrera, Laura C Bonifaz, Gabriela Molina, Yolanda López-Vidal
Nontuberculous mycobacteria (NTM) are recognized as emerging pathogens and their immune regulatory mechanisms are not well described yet. From them, Mycobacterium avium is known to be a weak activator of dendritic cells (DCs) that impairs the response induced by BCG vaccine. However, whether other NTM such as Mycobacterium scrofulaceum may modulate the activation of DCs, has not been extensively studied. Here, we exposed bone marrow-derived DCs (BMDCs) to M. scrofulaceum and we analyzed the effect on the activation of DCs...
July 2016: Tuberculosis
K Afsal, P Selvaraj
1,25-dihydroxyvitamin D3 [1,25(OH)2D3] is a powerful immuno-modulator, which enhances expression of antimicrobial peptides and induces autophagy in monocytes/macrophages. Since 1,25(OH)2D3 increases the phagocytic potential of monocytes/macrophages, we have explored the effect of 1,25(OH)2D3 on the expression of receptors such as mannose receptor (CD206) and DC-SIGN (CD209) as well as autophagy genes such as ATG5 and Beclin-1 (BECN1) in monocytes/macrophages of healthy controls (HCs) and pulmonary tuberculosis (PTB) patients with and without cavitary disease...
July 2016: Tuberculosis
Li Ma, Jian Fei, Ying Chen, Bing Zhao, Zhi-Tao Yang, Lu Wang, Hui-Qiu Sheng, Er-Zhen Chen, En-Qiang Mao
BACKGROUND: The expression of dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) in renal tubular epithelial cells has been thought to be highly correlated with the occurrence of several kidney diseases, but whether it takes place in renal tissues during hemorrhagic shock (HS) is unknown. The present study aimed to investigate this phenomenon and the inhibitory effect of Vitamin C (VitC). METHODS: A Sprague-Dawley rat HS model was established in vivo in this study...
July 20, 2016: Chinese Medical Journal
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