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membrane vesicles derived from Streptococcus suis serotype 2 induce cell pyroptosis in endothelial cells via the NLRP3/Caspase-1/GSDMD pathway

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Journal of Integrative Agriculture 2024年第4期23卷 1338-1353页

作者： Keda Shi Yan Li Minsheng Xu Kunli Zhang Hongchao Gou Chunling Li Shaolun Zhai Institute of Animal Health Guangdong Academy of Agricultural Sciences/Key Laboratory of Livestock Disease Prevention ofGuangdong Province/Scientific Observation and Experiment Station of Veterinary Drugs and Diagnostic Techniques of GuangdongProvinceMinistry of Agriculture and Rural AffairsGuangzhou 510640China Maoming Branch Guangdong Laboratory for Lingnan Modern Agricultural Science and TechnologyMaoming 525000China College of Animal Science&Technology Zhongkai University of Agriculture and EngineeringGuangzhou 510225China

Streptococcus suis serotype 2(S.suis 2)is a zoonotic pathogen that clinically causes severe swine and human infections(such as meningitis,endocarditis,and septicemia).In order to cause widespread diseases in different organs,S.suis 2 must colonize the host,break the blood barrier,and cause exaggerated inflammation.In the last few years,most studies have focused on a single virulence factor and its influences on the host.membrane vesicles(MVs)can be actively secreted into the extracellular environment contributing to bacteria-host interactions.Gram-negative bacteria-derived outer membrane vesicles(OMVs)were recently shown to activate host Caspase-11-mediated non-canonical inflammasome pathway via deliverance of OMV-bound lipopolysaccharide(LPS),causing host cell pyroptosis.However,little is known about the effect of the MVs from S.suis 2(Gram-positive bacteria without LPS)on cell pyroptosis.Thus,we investigated the molecular mechanism by which S.suis 2 MVs participate in endothelial cell pyroptosis.In this study,we used proteomics,electron scanning microscopy,fluorescence microscope,Western blotting,and bioassays,to investigate the MVs secreted by S.suis 2.First,we demonstrated that S.suis 2 secreted MVs with an average diameter of 72.04 nm,and 200 proteins in MVs were identified.Then,we showed that MVs were transported to cells via mainly dynamin-dependent endocytosis.The S.suis 2 MVs activated NLRP3/Caspase-1/GSDMD canonical inflammasome signaling pathway,resulting in cell pyroptosis,but it did not activate the Caspase-4/-5 pathway.More importantly,endothelial cells produce large amounts of reactive oxygen species(ROS)and lost their mitochondrial membrane potential under induction by S.suis 2 MVs.The results in this study suggest for the first time that MVs from S.suis 2 were internalized by endothelial cells via mainly dynamin-dependent endocytosis and might promote NLRP3/Caspase-1/GSDMD pathway by mitochondrial damage,which produced mtDNA and ROS under induction,leading to the pyroptosis of endothelial cells.

关键词： Streptococcus suis serotype 2 membrane vesicles endocytosis pyroptosis NLRP3 inflammasomes mitochondrial damage endothelial cell

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Bacterial extracellular vesicle applications in cancer immunotherapy

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Bioactive Materials 2023年第4期22卷 551-566页

作者： Kanika Suri Anisha D’Souza Di Huang Aashray Bhavsar Mansoor Amiji Department of Bioengineering College of EngineeringNortheastern UniversityBostonMA02115USA Department of Pharmaceutical Sciences School of PharmacyNortheastern UniversityBostonMA02115USA Massachusetts Eye and Ear Infirmary Harvard Medical SchoolBostonMA20115USA Department of Chemical Engineering College of EngineeringNortheastern UniversityBostonMA02115USA

Cancer therapy is undergoing a paradigm shift toward immunotherapy focusing on various approaches to activate the host immune system.As research to identify appropriate immune cells and activate anti-tumor immunity continues to expand,scientists are looking at microbial sources given their inherent ability to elicit an immune response.Bacterial extracellular vesicles(BEVs)are actively studied to control systemic humoral and cellular immune responses instead of using whole microorganisms or other types of extracellular vesicles(EVs).BEVs also provide the opportunity as versatile drug delivery carriers.Unlike mammalian EVs,BEVs have already made it to the clinic with the meningococcal vaccine(Bexsero®).However,there are still many unanswered questions in the use of BEVs,especially for chronic systemically administered immunotherapies.In this review,we address the opportunities and challenges in the use of BEVs for cancer immunotherapy and provide an outlook towards development of BEV products that can ultimately translate to the clinic.

关键词： Cancer immunotherapy Bacterial extracellular vesicles membrane vesicles Outer membrane vesicles Mammalian extracellular vesicles

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