laminaran and HIV-Infections

1,3-β-Glucans are a class of natural polysaccharides with unique pharmacological properties and the ability to form single- and triple-helical structures that can be formed into resilient gels with the application of heat and humidity. The pharmacological capabilities of 1,3-β-glucans include the impartation of tumor inhibition, resistance to infectious disease, and improvements in wound healing. Curdlan is a linear 1,3-β-glucan that has been used extensively to study the nature of these helical structures and gels, and Curdlan sulfates have found ongoing application in the inhibition of HIV infection. 1,3-β-Glucan gels have been used in food science as stabilizers and encapsulating agents, in nanoscience as scaffolds to build nanofibers and nanowires, and in drug delivery to form nanoparticles and create helical micelles encapsulating polynucleotides. 1,3-β-Glucans are beginning to have enormous significance due to their dual nature as structure-forming agents and pharmacological substances, and research is especially focused on the application of these polymers in animal nutrition and drug delivery.

Topics: Animals; Anti-Infective Agents; Anticarcinogenic Agents; beta-Glucans; Carbohydrate Conformation; Drug Delivery Systems; Gels; HIV Infections; Hot Temperature; Humans; Immunologic Factors; Molecular Structure; Polysaccharides, Bacterial; Wound Healing

Natural killer (NK) cells use the activating receptor NKp30 as a microbial pattern-recognition receptor to recognize, activate cytolytic pathways, and directly kill the fungi Cryptococcus neoformans and Candida albicans. However, the fungal pathogen-associated molecular pattern (PAMP) that triggers NKp30-mediated killing remains to be identified. Here we show that β-1,3-glucan, a component of the fungal cell wall, binds to NKp30. We further demonstrate that β-1,3-glucan stimulates granule convergence and polarization, as shown by live cell imaging. Through Src Family Kinase signaling, β-1,3-glucan increases expression and clustering of NKp30 at the microbial and NK cell synapse to induce perforin release for fungal cytotoxicity. Rather than blocking the interaction between fungi and NK cells, soluble β-1,3-glucan enhances fungal killing and restores defective cryptococcal killing by NK cells from HIV-positive individuals, implicating β-1,3-glucan to be both an activating ligand and a soluble PAMP that shapes NK cell host immunity.

Topics: beta-Glucans; Candida albicans; Cell Line; Cell Polarity; Cryptococcus neoformans; Cytoplasmic Granules; Cytotoxicity, Immunologic; HIV Infections; Host-Pathogen Interactions; Humans; Immunological Synapses; Killer Cells, Natural; Ligands; Microscopy, Atomic Force; Natural Cytotoxicity Triggering Receptor 3; Pathogen-Associated Molecular Pattern Molecules; Perforin; Recombinant Proteins; Solubility