Browsing by MeSH term "Polysaccharides"
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Publication Capsule enlargement in Cryptococcus neoformans confers resistance to oxidative stress suggesting a mechanism for intracellular survival(Wiley, 2008-10) Zaragoza, Oscar; Chrisman, Cara J; Castelli, Maria Victoria; Frases, Susana; Cuenca-Estrella, Manuel; Rodriguez-Tudela, Juan Luis; Casadevall, Arturo; Ministerio de Educación y Ciencia (España); Instituto de Salud Carlos IIICryptococcus neoformans is a facultative intracellular pathogen. The most distinctive feature of C. neoformans is a polysaccharide capsule that enlarges depending on environmental stimuli. The mechanism by which C. neoformans avoids killing during phagocytosis is unknown. We hypothesized that capsule growth conferred resistance to microbicidal molecules produced by the host during infection, particularly during phagocytosis. We observed that capsule enlargement conferred resistance to reactive oxygen species produced by H(2)O(2) that was not associated with a higher catalase activity, suggesting a new function for the capsule as a scavenger of reactive oxidative intermediates. Soluble capsular polysaccharide protected C. neoformans and Saccharomyces cerevisiae from killing by H(2)O(2). Acapsular mutants had higher susceptibility to free radicals. Capsular polysaccharide acted as an antioxidant in the nitroblue tetrazolium (NBT) reduction coupled to beta-nicotinamide adenine dinucleotide (NADH)/phenazine methosulfate (PMS) assay. Capsule enlargement conferred resistance to antimicrobial peptides and the antifungal drug Amphotericin B. Interestingly, the capsule had no effect on susceptibility to azoles and increased susceptibility to fluconazole. Capsule enlargement reduced phagocytosis by environmental predators, although we also noticed that in this system, starvation of C. neoformans cells produced resistance to phagocytosis. Our results suggest that capsular enlargement is a mechanism that enhances C. neoformans survival when ingested by phagocytic cells.Publication Characterization of broadly neutralizing antibody responses to HIV-1 in a cohort of long term non-progressors(Public Library of Science (PLOS), 2018-03-20) Gonzalez-Fernandez, Nuria; McKee, Krisha; Lynch, Rebecca M; Georgiev, Ivelin S; Jimenez, Laura; Grau, Eulalia; Yuste-Herranz, Maria Eloisa; Kwong, Peter D; Mascola, John R; Alcamí, José; Instituto de Salud Carlos III; European Regional Development Fund; Fundación para la Investigación y la Prevención del Sida en EspañaBACKGROUND: Only a small fraction of HIV-1-infected patients develop broadly neutralizing antibodies (bNAbs), a process generally associated to chronic antigen stimulation. It has been described that rare aviremic HIV-1-infected patients can generate bNAbs but this issue remains controversial. To address this matter we have assessed bNAb responses in a large cohort of long-term non-progressors (LTNPs) with low or undetectable viremia. METHODS: Samples from the LTNP cohort of the Spanish AIDS Research Network (87 elite and 42 viremic controllers) and a control population of 176 viremic typical-progressors (TPs) were screened for bNAbs using Env-recombinant viruses. bNAb specificities were studied by ELISA using mutated gp120, neutralization assays with mutated viruses, and peptide competition. Epitope specificities were also elucidated from the serum pattern of neutralization against a panel of diverse HIV-1 isolates. RESULTS: Broadly neutralizing sera were found among 9.3% LTNPs, both elite (7%) and viremic controllers (14%). Within the broadly neutralizing sera, CD4 binding site antibodies were detected by ELISA in 4/12 LTNPs (33%), and 16/33 of TPs (48%). Anti-MPER antibodies were detected in 6/12 LTNPs (50%) and 14/33 TPs (42%) whereas glycan-dependent HIV-1 bNAbs were more frequent in LTNPs (11/12, 92%) as compared to TPs (12/33, 36%). A good concordance between standard serum mapping and neutralization-based mapping was observed. CONCLUSION: LTNPs, both viremic and elite controllers, showed broad humoral immune responses against HIV-1, including activity against many major epitopes involved in bNAbs-mediated protection.Publication Heat inactivated mycobacteria, alpha-Gal and zebrafish: Insights gained from experiences with two promising trained immunity inductors and a validated animal model(Wiley, 2022-10) Juste, Ramón A; Ferreras-Colino, Elisa; de la Fuente, José; Dominguez-Rodriguez, Mercedes; Risalde, María A; Domínguez, Lucas; Cabezas-Cruz, Alejandro; Gortázar, Christian; Regional Government of Castile-La Mancha (España); Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF); Ministerio de Ciencia e Innovación (España); Agencia Estatal de Investigación (España); Gobierno del Principado de Asturias (España); Unión Europea. Fondo Social Europeo (ESF/FSE)Trained immunity (TRAIM) may be defined as a form of memory where innate immune cells such as monocytes, macrophages, dendritic and natural killer (NK) cells undergo an epigenetic reprogramming that enhances their primary defensive capabilities. Cross-pathogen protective TRAIM can be triggered in different hosts by exposure to live microbes or microbe-derived products such as heat-inactivated Mycobacterium bovis or with the glycan α-Gal to elicit protective responses against several pathogens. We review the TRAIM paradigm using two models representing distinct scales of immune sensitization: the whole bacterial cell and one of its building blocks, the polysaccharides or glycans. Observations point out to macrophage lytic capabilities and cytokine regulation as two key components in non-specific innate immune responses against infections. The study of the TRAIM response deserves attention to better characterize the evolution of host-pathogen cooperation both for identifying the aetiology of some diseases and for finding new therapeutic strategies. In this field, the zebrafish provides a convenient and complete biological system that could help to deepen in the knowledge of TRAIM-mediated mechanisms in pathogen-host interactions.Publication Immunomodulatory, Antioxidant Activity and Cytotoxic Effect of Sulfated Polysaccharides from Porphyridium cruentum. (S.F.Gray) Nägeli.(2021-03-24) Casas-Arrojo, Virginia; Decara, Juan; de Los Ángeles Arrojo-Agudo, María; Pérez-Manríquez, Claudia; Abdala-Díaz, Roberto TPorphyridium cruentum is a unicellular microalga that can synthesize and secrete to the culture medium-high amounts of polysaccharides. In this study, the immunomodulatory, cytotoxic effect and antioxidant activity of the sulfated polysaccharides (PcSPs) were determinate. The PcSPs were precipitated with 2% Cetylpyridinium bromide hydrate and ethanol and purified by dialysis. The extract was lyophilized for its characterization by Fourier transform-Infrared (FT-IR) spectroscopy and gas chromatography-mass spectrometry (GC-MS). The antioxidant activity of PcSPs were examined with assay 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) and compared with that of the biomass, observing significant differences between the results obtained from the PcSPs and biomass. To determine their ability to induce cytokine production Tumor Necrosis Factor alpha (TNF-α) and interleukina-6 (IL-6), the immunomodulatory activity of the PcSPs has been evaluated. In the mouse macrophage cell line (RAW 264.7), PcSPs are potent inducers of IL-6 cytokines but mainly of TNF-α. The cytotoxic capacity of PcSPs was measured by the MTT colorimetric assay in colorectal carcinoma (HTC-116), human leukemia (U-937 and HL-60), breast cancer (MCF-7), lung cancer (NCI-H460) and human gingival fibroblasts (HGF-1) cell lines. The IC50 value of 2311.20 µg mL-1, 1676.74 µg mL-1, 1089.63 µg mL-1, 5498.14 µg mL-1 and 2861.49 µg mL-1 respectively in the tumor lines and 5022.55 µg mL-1 in gingival fibroblasts were obtained. Our study suggested that PcSPs from P. cruentum have a moderate immunomodulatory and cytotoxic effect. The results obtained indicate that the polysaccharides from P. cruentum are potent inducers of IL-6 cytokines and, most importantly, of TNF-α. PcSPs showed no evidence of antigenic activity or hypersensitivity when administered intraperitoneally in mice. Furthermore, the in vivo study revealed an improvement of local inflammatory response against stress in the peritoneum. These findings suggest that the PcSPs from P. cruentum might have potential as a valuable ingredient in nutraceutical products.Publication Recent advances on smart glycoconjugate vaccines in infections and cancer.(2021-06-01) Anderluh, Marko; Berti, Francesco; Bzducha-Wróbel, Anna; Chiodo, Fabrizio; Colombo, Cinzia; Compostella, Federica; Durlik, Katarzyna; Ferhati, Xhenti; Holmdahl, Rikard; Jovanovic, Dragana; Kaca, Wieslaw; Lay, Luigi; Marinovic-Cincovic, Milena; Marradi, Marco; Ozil, Musa; Polito, Laura; Reina, Josè Juan; Reis, Celso A; Sackstein, Robert; Silipo, Alba; Švajger, Urban; Vaněk, Ondřej; Yamamoto, Fumiichiro; Richichi, Barbara; van Vliet, Sandra JVaccination is one of the greatest achievements in biomedical research preventing death and morbidity in many infectious diseases through the induction of pathogen-specific humoral and cellular immune responses. Currently, no effective vaccines are available for pathogens with a highly variable antigenic load, such as the human immunodeficiency virus or to induce cellular T-cell immunity in the fight against cancer. The recent SARS-CoV-2 outbreak has reinforced the relevance of designing smart therapeutic vaccine modalities to ensure public health. Indeed, academic and private companies have ongoing joint efforts to develop novel vaccine prototypes for this virus. Many pathogens are covered by a dense glycan-coat, which form an attractive target for vaccine development. Moreover, many tumor types are characterized by altered glycosylation profiles that are known as "tumor-associated carbohydrate antigens". Unfortunately, glycans do not provoke a vigorous immune response and generally serve as T-cell-independent antigens, not eliciting protective immunoglobulin G responses nor inducing immunological memory. A close and continuous crosstalk between glycochemists and glycoimmunologists is essential for the successful development of efficient immune modulators. It is clear that this is a key point for the discovery of novel approaches, which could significantly improve our understanding of the immune system. In this review, we discuss the latest advancements in development of vaccines against glycan epitopes to gain selective immune responses and to provide an overview on the role of different immunogenic constructs in improving glycovaccine efficacy.Publication Two genomic regions encoding exopolysaccharide production systems have complementary functions in B. cereus multicellularity and host interaction(Springer, 2020-01-22) Caro-Astorga, Joaquin; Álvarez-Mena, Ana; Hierrezuelo, Jesús; Guadix, Juan Antonio; Heredia-Ponce, Zahira; Arboleda-Estudillo, Yohanna; González-Munoz, Elena; de Vicente, Antonio; Romero, Diego; [Caro-Astorga,J; Álvarez-Mena,A; Hierrezuelo,J; Heredia-Ponce,Z; de Vicente,A; Romero,D] Instituto de Hortofruticultura Subtropical y Mediterránea “La Mayora” –Departamento de Microbiología, Universidad de Málaga, Málaga, Spain. [Guadix,JA] Departamento de Biología Animal, Facultad de Ciencias, Universidad de Málaga - IBIMA, Málaga, Spain. [Guadix,JA] Centro Andaluz de Nanomedicina y Biotecnología (BIONAND), Junta de Andalucía, Universidad de Málaga, Campanillas (Málaga), Spain. [Arboleda-Estudillo,Y; González-Munoz,E] LARCEL, Andalusian Laboratory of Cell Reprogramming, Andalusian Center for Nanomedicine and Biotechnology-BIONAND, Málaga, Spain.Bacterial physiology and adaptation are influenced by the exopolysaccharides (EPS) they produce. These polymers are indispensable for the assembly of the biofilm extracellular matrix in multiple bacterial species. In a previous study, we described the profound gene expression changes leading to biofilm assembly in B. cereus ATCC14579 (CECT148). We found that a genomic region putatively dedicated to the synthesis of a capsular polysaccharide (eps2) was overexpressed in a biofilm cell population compared to in a planktonic population, while we detected no change in the transcript abundance from another genomic region (eps1) also likely to be involved in polysaccharide production. Preliminary biofilm assays suggested a mild role for the products of the eps2 region in biofilm formation and no function for the products of the eps1 region. The aim of this work was to better define the roles of these two regions in B. cereus multicellularity. We demonstrate that the eps2 region is indeed involved in bacterial adhesion to surfaces, cell-to-cell interaction, cellular aggregation and biofilm formation, while the eps1 region appears to be involved in a kind of social bacterial motility. Consistent with these results, we further demonstrate using bacterial-host cell interaction experiments that the eps2 region is more relevant to the adhesion to human epithelial cells and the zebrafish intestine, suggesting that this region encodes a bacterial factor that may potentiate gut colonization and enhance pathogenicity against humans.