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6. Transcriptional and functional insights into the host immune response against the emerging fungal pathogen Candida auris

Author

Bruno, Mariolina, Kersten, Simone, Bain, Judith M., Jaeger, Martin, Rosati, Diletta, Kruppa, Michael D., Lowman, Douglas W., Rice, Peter J., Graves, Bridget, Ma, Zuchao, Jiao, Yue Ning, Chowdhary, Anuradha, Renieris, George, van de Veerdonk, Frank L., Kullberg, Bart-Jan, Giamarellos-Bourboulis, Evangelos J., Hoischen, Alexander, Gow, Neil A. R., Brown, Alistair J. P., Meis, Jacques F., Williams, David L., and Netea, Mihai G.

Published
2020
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7. Carbohydrates from Pseudomonas aeruginosa biofilms interact with immune C-type lectins and interfere with their receptor function

Author

Singh, Sonali, Almuhanna, Yasir, Alshahrani, Mohammad Y., Lowman, Douglas W., Rice, Peter J., Gell, Chris, Ma, Zuchao, Graves, Bridget, Jackson, Darryl, Lee, Kelly, Juarez, Rucha, Koranteng, Janice, Muntaka, Sirina, Daniel A. Mitchell, da Silva, Ana C., Hussain, Farah, Yilmaz, Gokhan, Mastrotto, Francesca, Irie, Yasuhiko, Williams, Paul, Williams, David L., Cámara, Miguel, and Martinez-Pomares, Luisa

Published
2021
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8. Self‐recognition through Dectin‐1 exacerbates liver inflammation.

Author

Torigoe, Shota, Lowman, Douglas W., Sugiki, Toshihiko, Williams, David L., and Yamasaki, Sho

Subjects
*HEPATITIS, *LECTINS, *HEPATIC fibrosis, *HIGH-fat diet, *LIVER diseases, *IMMUNE response
Abstract

Dectin‐1 is a well‐characterized C‐type lectin receptor involved in anti‐fungal immunity through the recognition of polysaccharides; however, molecular mechanisms and outcomes initiated through self‐recognition have not been fully understood. Here, we purified a water‐soluble fraction from mouse liver that acts as a Dectin‐1 agonist. To address the physiological relevance of this recognition, we utilized sterile liver inflammation models. The CCl4‐induced hepatitis model showed that Dectin‐1 deficiency led to reduced inflammation through decreased inflammatory cell infiltration and lower pro‐inflammatory cytokine levels. Moreover, in a NASH model induced by streptozotocin and a high‐fat diet, hepatic inflammation and fibrosis were ameliorated in Dectin‐1‐deficient mice. The Dectin‐1 agonist activity was increased in the water‐soluble fraction from NASH mice, suggesting a potential pathogenic cycle between Dectin‐1 activation and hepatitis progression. In vivo administration of the fraction into mice induced hepatic inflammation. These results highlight a role of self‐recognition through Dectin‐1 that triggers hepatic innate immune responses and contributes to the exacerbation of inflammation in pathogenic settings. Thus, the blockade of this axis may provide a therapeutic option for liver inflammatory diseases. [ABSTRACT FROM AUTHOR]

Published
2024
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9. An adjuvant strategy enabled by modulation of the physical properties of microbial ligands expands antigen immunogenicity

Author

Borriello, Francesco, primary, Poli, Valentina, additional, Shrock, Ellen, additional, Spreafico, Roberto, additional, Liu, Xin, additional, Pishesha, Novalia, additional, Carpenet, Claire, additional, Chou, Janet, additional, Di Gioia, Marco, additional, McGrath, Marisa E., additional, Dillen, Carly A., additional, Barrett, Nora A., additional, Lacanfora, Lucrezia, additional, Franco, Marcella E., additional, Marongiu, Laura, additional, Iwakura, Yoichiro, additional, Pucci, Ferdinando, additional, Kruppa, Michael D., additional, Ma, Zuchao, additional, Lowman, Douglas W., additional, Ensley, Harry E., additional, Nanishi, Etsuro, additional, Saito, Yoshine, additional, O’Meara, Timothy R., additional, Seo, Hyuk-Soo, additional, Dhe-Paganon, Sirano, additional, Dowling, David J., additional, Frieman, Matthew, additional, Elledge, Stephen J., additional, Levy, Ofer, additional, Irvine, Darrell J., additional, Ploegh, Hidde L., additional, Williams, David L., additional, and Zanoni, Ivan, additional

Published
2022
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12. An adjuvant strategy enabled by modulation of the physical properties of fungal mannans elicits pan-coronavirus reactive anti-SARS-CoV-2 Spike antibodies

Author

Borriello, Francesco, primary, Spreafico, Roberto, additional, Poli, Valentina, additional, Shrock, Ellen, additional, Chou, Janet, additional, Barrett, Nora A., additional, Lacanfora, Lucrezia, additional, Franco, Marcella E., additional, Marongiu, Laura, additional, Iwakura, Yoichiro, additional, Pucci, Ferdinando, additional, Kruppa, Michael D., additional, Ma, Zuchao, additional, Lowman, Douglas W., additional, Ensley, Harry E., additional, Nanishi, Etsuro, additional, Saito, Yoshine, additional, O’Meara, Timothy R., additional, Seo, Hyuk-Soo, additional, McGrath, Marisa E., additional, Logue, James, additional, Haupt, Robert E., additional, Dhe-Paganon, Sirano, additional, Dowling, David J., additional, Frieman, Matthew, additional, Elledge, Stephen J., additional, Levy, Ofer, additional, Irvine, Darrell J., additional, Williams, David L., additional, and Zanoni, Ivan, additional

Published
2021
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18. Immunoregulatory activity of the natural product laminarin varies widely as a result lt of its physical properties1

Author

Smith, Alyson J., Graves, Bridget, Child, Robert, Rice, Peter J., Ma, Zuchao, Lowman, Douglas W., Ensley, Harry E., Ryter, Kendal T., Evans, Jay T., and Williams, David L.

Subjects
Biological Products, Polymers, Macrophages, Proton Magnetic Resonance Spectroscopy, Article, Recombinant Proteins, Cell Line, Immunomodulation, Mice, Gene Knockdown Techniques, Leukocytes, Mononuclear, Animals, Cytokines, Humans, Immunologic Factors, Lectins, C-Type, Glucans, Protein Binding
Abstract

Ligation of Dectin-1 by fungal glucans elicits a Th17 response that is necessary for clearing many fungal pathogens. Laminarin is a (1→3, 1→6)-β-glucan that is widely reported to be a Dectin-1 antagonist, however, there are reports that laminarin is also a Dectin-1 agonist. To address this controversy, we assessed the physical properties, structure, purity, Dectin-1 binding, and biological activity of five different laminarin preparations from three different commercial sources. The proton nuclear magnetic resonance analysis indicated that all of the preparations contained laminarin although their molecular mass varied considerably (4400-34,400 Da). Two of the laminarins contained substantial quantities of very low m.w. compounds, some of which were not laminarin. These low m.w. moieties could be significantly reduced by extensive dialysis. All of the laminarin preparations were bound by recombinant human Dectin-1 and mouse Dectin-1, but the affinity varied considerably, and binding affinity did not correlate with Dectin-1 agonism, antagonism, or potency. In both human and mouse cells, two laminarins were Dectin-1 antagonists and two were Dectin-1 agonists. The remaining laminarin was a Dectin-1 antagonist, but when the low m.w. moieties were removed, it became an agonist. We were able to identify a laminarin that is a Dectin-1 agonist and a laminarin that is Dectin-1 antagonist, both of which are relatively pure preparations. These laminarins may be useful in elucidating the structure and activity relationships of glucan/Dectin-1 interactions. Our data demonstrate that laminarin can be either a Dectin-1 antagonist or agonist, depending on the physicochemical properties, purity, and structure of the laminarin preparation employed.

Published
2017

20. Leishmania braziliensisenhances monocyte responses to promote anti-tumor activity

Author

dos Santos, Jéssica Cristina, Moreno, María, Teufel, Lisa U., Chilibroste, Sofía, Keating, Samuel T., Groh, Laszlo, Domínguez-Andrés, Jorge, Williams, David L., Ma, Zuchao, Lowman, Douglas W., Ensley, Harry E., Novakovic, Boris, Ribeiro-Dias, Fátima, Netea, Mihai G., Chabalgoity, José A., and Joosten, Leo A.B.

Abstract

Innate immune cells can undergo long-term functional reprogramming after certain infections, a process called trained immunity (TI). Here, we focus on antigens of Leishmania braziliensis, which induced anti-tumor effects via trained immunity in human monocytes. We reveal that monocytes exposed to promastigote antigens of L. braziliensisdevelop an enhanced response to subsequent exposure to Toll-like receptor (TLR)2 or TLR4 ligands. Mechanistically, the induction of TI in monocytes by L. braziliensisis mediated by multiple pattern recognition receptors, changes in metabolism, and increased deposition of H3K4me3 at the promoter regions of immune genes. The administration of L. braziliensisexerts potent anti-tumor capabilities by delaying tumor growth and prolonging survival of mice with non-Hodgkin lymphoma. Our work reveals mechanisms of TI induced by L. braziliensis in vitroand identifies its potential for cancer immunotherapy.

Published
2024
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25. Engineering Nanogels for Drug Delivery to Pathogenic Fungi Aspergillus fumigatusby Tuning Polymer Amphiphilicity

Author

Horvat, Sonja, Yu, Yidong, Böjte, Szalbolcs, Teßmer, Ingrid, Lowman, Douglas W., Ma, Zuchao, Williams, David L., Beilhack, Andreas, Albrecht, Krystyna, and Groll, Jürgen

Abstract

Invasive aspergillosis is a serious threat to immunodeficient and critically ill patients caused mainly by the fungus Aspergillus fumigatus. Here, poly(glycidol)-based nanogels (NGs) are proposed as delivery vehicles for antifungal agents for sustained drug release. NGs are formed by simple self-assembly of random copolymers, followed by oxidative cross-linking of thiol functionalities. We investigate the impact of copolymer amphiphilicity on NG interaction with mature fungal hyphae in order to select the optimal drug delivery system for model antifungal drug amphotericin B. The results show that drug-loaded NGs decrease minimal inhibitory concentration (MIC) for around four times and slow down the fungal biofilm synthesis at concentrations lower than MIC. Our results suggest that amphiphilicity of nanoparticle’s polymer matrix is an important factor in understanding the action of nanocarriers toward fungal cells and should be considered in the development of nanoparticle-based antifungal therapy.

Published
2024
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26. Novel Structural Features in Candida albicans Hyphal Glucan Provide a Basis for Differential Innate Immune Recognition of Hyphae Versus Yeast

Author

Lowman, Douglas W., primary, Greene, Rachel R., additional, Bearden, Daniel W., additional, Kruppa, Michael D., additional, Pottier, Max, additional, Monteiro, Mario A., additional, Soldatov, Dmitriy V., additional, Ensley, Harry E., additional, Cheng, Shih-Chin, additional, Netea, Mihai G., additional, and Williams, David L., additional

Published
2014
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28. The Mnn2 Mannosyltransferase Family Modulates Mannoprotein Fibril Length, Immune Recognition and Virulence of Candida albicans

Author

Hall, Rebecca A., primary, Bates, Steven, additional, Lenardon, Megan D., additional, MacCallum, Donna M., additional, Wagener, Jeanette, additional, Lowman, Douglas W., additional, Kruppa, Michael D., additional, Williams, David L., additional, Odds, Frank C., additional, Brown, Alistair J. P., additional, and Gow, Neil A. R., additional

Published
2013
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34. Differential High-Affinity Interaction of Dectin-1 with Natural or Synthetic Glucans Is Dependent upon Primary Structure and Is Influenced by Polymer Chain Length and Side-Chain Branching

Author

Adams, Elizabeth L., primary, Rice, Peter J., additional, Graves, Bridget, additional, Ensley, Harry E., additional, Yu, Hai, additional, Brown, Gordon D., additional, Gordon, Siamon, additional, Monteiro, Mario A., additional, Papp-Szabo, Erzsebet, additional, Lowman, Douglas W., additional, Power, Trevor D., additional, Wempe, Michael F., additional, and Williams, David L., additional

Published
2008
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37. New Insights into the Structure of (1→3,1→6)-β-DGlucan Side Chains in the Candida glabrata Cell Wall.

Author

Lowman, Douglas W., West, Lara J., Bearden, Daniel W., Wempe, Michael F., Power, Trevor D., Ensley, Harry E., Haynes, Ken, Williams, David L., and Kruppa, Michael D.

Subjects
*GLUCANS, *CANDIDA, *FUNGAL cell walls, *POLYMERS, *PROTEINS, *POLYSACCHARIDES
Abstract

β-glucan is a (1→3)-β-linked glucose polymer with (1→6)-β-linked side chains and a major component of fungal cell walls. β-glucans provide structural integrity to the fungal cell wall. The nature of the (1-6)-β-linked side chain structure of fungal (1→3,1→6)-β-D-glucans has been very difficult to elucidate. Herein, we report the first detailed structural characterization of the (1→6)-β-linked side chains of Candida glabrata using high-field NMR. The (1→6)-β-linked side chains have an average length of 4 to 5 repeat units spaced every 21 repeat units along the (1→3)-linked polymer backbone. Computer modeling suggests that the side chains have a bent curve structure that allows for a flexible interconnection with parallel (1→3)-β-Dglucan polymers, and/or as a point of attachment for proteins. Based on these observations we propose new approaches to how (1→6)-β-linked side chains interconnect with neighboring glucan polymers in a manner that maximizes fungal cell wall strength, while also allowing for flexibility, or plasticity. [ABSTRACT FROM AUTHOR]

Published
2011
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38. Marine yeast diet confers better protection than its cell wall component (1-3)-β-d-glucan as an immunostimulant in Fenneropenaeus indicus.

Author

Sajeevan, Thavarool Puthiyedathu, Lowman, Douglas W., Williams, David L., Selven, Subramanian, Anas, Abdulaziz, and Rosamma, Philip

Subjects
*YEAST, *NUTRITION, *IMMUNOLOGICAL adjuvants, *METALLOENZYMES, *NUCLEIC acids
Abstract

A comparative study was performed to evaluate the immunostimulatory effect of yeast and yeast-derived glucan in white prawn Fenneropenaeus indicus (sub-adults of ∼20 gm). Feed with a whole cell biomass of marine yeast Candida sake S165 (CSY) at a concentration of 10% (w/w) and another feed with 0.2% glucan of C. sake S165 (CSG) were used in the study. Fenneropenaeus indicus were fed with these diets for 40 days and subsequently challenged with the white spot syndrome virus (WSSV). Haematological parameters such as the total haemocyte count, phenoloxidase activity, superoxide anion (O2−) level, haemolymph peroxidase level and post-challenge survival against WSSV infection were determined to assess the immune status. In the present experiment, a higher immunity index and post-challenge survival were recorded in shrimps fed with the whole cell yeast diet. The better immunostimulatory performance of the whole cell yeast diet compared with the glucan diet could be attributed to the cellular constituents of yeast including the cell wall glucan, nucleotides, carotenoid pigments and vitamins. Here we observed that whole cell yeast performed better as an immunostimulant than the extracted cell wall glucans. Therefore, the use of yeast biomass in diets, rather than the yeast cell wall extract, glucan, would confer better protection against microbial infection besides reducing the cost of shrimp production. [ABSTRACT FROM AUTHOR]

Published
2009
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39. Alkali insoluble glucan extracted from Acremonium diospyri is a more potent immunostimulant in the Indian White Shrimp, Fenneropenaeus indicus than alkali soluble glucan.

Author

Anas, Abdulaziz, Lowman, Douglas W, Williams, David L, Millen, Stewart, Pai, Srinivas Somnath, Sajeevan, Thavarool Puthiyedathu, Philip, Rosamma, and Singh, Isaac Sarojeni Bright

Subjects
*AQUACULTURE, *GLUCANS, *ACREMONIUM, *PENAEUS schmitti, *REDTAIL prawn
Abstract

Effect of an extraction method on the structure of glucan and its immunostimulatory response in Fenneropenaeus indicus was investigated. Here we extracted alkali insoluble glucan (AIG) and alkali soluble glucan (ASG) from a filamentous fungi Acremonium diospyri following alkali–acid hydrolysis and the sodium hypochlorite oxidation and dimethyl sulphoxide extraction method respectively. Structural analysis showed that 85% of glucan in AIG was a (1→3)-β-d-glucan and it increased the prophenoloxidase and reactive oxygen intermediate activity when administered to F. indicus. On the other hand, ASG, which contained 93% (1→3)-α-glucan, did not induce significant immune response in shrimp. Here we report that the difference in immunostimulatory potential between AIG and ASG is due to the difference in the percentage of (1→3)-β-d-glucans present in each preparation, which varies with the method of extraction employed. Also our observations suggest that glucan can be used as a potential immunostimulant to shrimp, provided it contains (1→3)-β-d-glucan as the major fraction. [ABSTRACT FROM AUTHOR]

Published
2009
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