Project description:Durvillaea antarctica (Fucales, Phaeophyceae) is a large kelp of high ecological and economic significance in the Southern Hemisphere. In natural beds along the central coast of Chile (Pacific Ocean), abnormal growth characterized by evident gall development and discolorations of the fronds/thallus was observed. Analysing these galls by light microscopy and scanning electron microscopy revealed the presence of endophytic eukaryotes showing typical characteristics for phytomyxean parasites. The parasite developed within enlarged cells of the subcortical tissue of the host. Multinucleate plasmodia developed into many, single resting spores. The affiliation of this parasite to the Phytomyxea (Rhizaria) was supported by 18S rDNA data, placing it within the Phagomyxida. Similar microorganisms were already reported once 23 years ago, indicating that these parasites are persistent and widespread in D. antarctica beds for long times. The symptoms caused by this parasite are discussed along with the ecological and economic consequences. Phytomyxean parasites may play an important role in the marine ecosystem, but they remain understudied in this environment. Our results demonstrate for the first time the presence of resting spores in Phagomyxida, an order in which resting spores were thought to be absent making this the first record of a phagomyxean parasite with a complete life cycle so far, challenging the existing taxonomic concepts within the Phytomyxea. The importance of the here described resting spores for the survival and ecology of the phagomyxid parasite will be discussed together with the impact this parasite may have on 'the strongest seaweed of the world', which is an important habitat forming and economic resource from the Southern Hemisphere.
Project description:An immunomodulatory polysaccharide (DAP4) was extracted, purified, and characterized from Durvillaea antarctica. The results of chemical and spectroscopic analyses demonstrated that the polysaccharide was a fucoidan, and was mainly composed of (1→3)-α-l-Fucp and (1→4)-α-l-Fucp residues with a small degree of branching at C-3 of (1→4)-α-l-Fucp residues. Sulfate groups were at C-4 of (1→3)-α-l-Fucp, C-2 of (1→4)-α-l-Fucp and minor C-6 of (1→4)-β-d-Galp. Small amounts of xylose and galactose exist in the forms of β-d-Xylp-(1→ and β-d-Gal-(1→. The immunomodulatory activity of DAP4 was measured on RAW 264.7 cells, the results proved that DAP4 exhibited excellent immunomodulatory activities, such as promoted the proliferation of spleen lymphocytes, increased NO production, as well as enhanced phagocytic of macrophages. Besides, DAP4 could also produce better enhancement on the vitality of NK cells. For the high immunomodulatory activity, DAP4 might be a potential source of immunomodulatory fucoidan with a novel structure.
Project description:Immunotherapy has emerged as a frontline approach in cancer management, aiming to enhance the adaptive immune response against tumors. However, its limited efficacy across a narrow range of tumor types necessitates the exploration of novel strategies that target innate immunity. Therapeutic modulation of pattern recognition receptors (PRRs) and innate immune cells holds promise in tumor eradication. β-glucan, a pathogen-associated molecular pattern (PAMP), acts as an immunostimulator, bridging the innate and adaptive immune responses. It exhibits low toxicity and high compatibility with various antitumor strategies. Plenty of clinical trials are ongoing to evaluate β-glucan-based cancer immunotherapy and shows promising clinical benefits across multiple cancer types. A soluble β-1,3/1,6-glucan with high purity from Durvillaea Antarctica (BG136) was reported previously by our group to exhibit pan antitumor effects alone as an immune stimulator. In current study, we proved the antitumor activity of BG136 in combination with anti-PD-1 antibodies in MC38 syngeneic tumor model in vivo. Integrated transcriptomic and metabolomic analyses suggest that BG136 enhances the antitumor immunity of anti-PD-1 antibodies by reprogramming tumor microenvironment to more proinflammatory status. There are more innate and adaptive immune cell infiltration and activation, enhanced lipid metabolism, decreased ascorbate and aldarate metabolism. These findings provide mechanistic insights supporting the potent antitumor efficacy of BG136 in combination with immune checkpoint inhibitor antibodies.
Project description:Immunotherapy has emerged as a frontline approach in cancer management, aiming to enhance the adaptive immune response against tumors. However, its limited efficacy across a narrow range of tumor types necessitates the exploration of novel strategies that target innate immunity. Therapeutic modulation of pattern recognition receptors (PRRs) and innate immune cells holds promise in tumor eradication. β-glucan, a pathogen-associated molecular pattern (PAMP), acts as an immunostimulator, bridging the innate and adaptive immune responses. It exhibits low toxicity and high compatibility with various antitumor strategies. Plenty of clinical trials are ongoing to evaluate β-glucan-based cancer immunotherapy and shows promising clinical benefits across multiple cancer types. A soluble β-1,3/1,6-glucan with high purity from Durvillaea Antarctica (BG136) was reported previously by our group to exhibit pan antitumor effects alone as an immune stimulator. In current study, we proved the antitumor activity of BG136 in combination with anti-PD-1 antibodies in MC38 syngeneic tumor model in vivo. Integrated transcriptomic and metabolomic analyses suggest that BG136 enhances the antitumor immunity of anti-PD-1 antibodies by reprogramming tumor microenvironment to more proinflammatory status. There are more innate and adaptive immune cell infiltration and activation, enhanced lipid metabolism, decreased ascorbate and aldarate metabolism. These findings provide mechanistic insights supporting the potent antitumor efficacy of BG136 in combination with immune checkpoint inhibitor antibodies.