Outer membrane vesicles of Glaesserlla parasuis activate the endosomal cGAS–STING–IRF3 pathway through nucleic acid payload delivery: a biological perspective on host defense protocol optimization
Abstract Glaesserlla parasuis (G. parasuis), a Gram-negative pathogen responsible for Glässer's disease, employs outer membrane vesicles (OMVs) as sophisticated nanoscale effectors to modulate host‒pathogen interplay. While bacterial OMVs are recognized as critical mediators of virulence dissem...
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2025-07-01
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| Series: | Veterinary Research |
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| Online Access: | https://doi.org/10.1186/s13567-025-01553-5 |
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| author | Kunli Zhang Zeyi Sun Xintong Kang Keda Shi Pinpin Chu Dongxia Yang Zhibiao Bian Yan Li Hongchao Gou Zhiyong Jiang Nanling Yang Xia Zhou Sutian Wang Zhanyong Wei Shaolun Zhai Huahua Kang Chunling Li |
| author_facet | Kunli Zhang Zeyi Sun Xintong Kang Keda Shi Pinpin Chu Dongxia Yang Zhibiao Bian Yan Li Hongchao Gou Zhiyong Jiang Nanling Yang Xia Zhou Sutian Wang Zhanyong Wei Shaolun Zhai Huahua Kang Chunling Li |
| author_sort | Kunli Zhang |
| collection | DOAJ |
| description | Abstract Glaesserlla parasuis (G. parasuis), a Gram-negative pathogen responsible for Glässer's disease, employs outer membrane vesicles (OMVs) as sophisticated nanoscale effectors to modulate host‒pathogen interplay. While bacterial OMVs are recognized as critical mediators of virulence dissemination, their functional orchestration in G. parasuis immunopathogenesis remains unclear. To date, few reports have focused on the relationships among G. parasuis, OMVs and host-susceptible cells; thus, more evidence is urgently needed to explore their crosstalk further. This study revealed a novel immune activation paradigm: both G. parasuis and its OMVs trigger robust type I interferon (IFN) responses via a DNA-sensing cascade. G. parasuis OMVs-Dio were internalized by macrophages in a time-dependent manner, partially via clathrin-mediated endocytosis but mainly via dynamin-dependent endocytosis. Studies have shown that IFNs play key antiviral roles in viral infections and important roles in bacterial infections. Our results suggested that IFNs inhibited G. parasuis adhesion and invasion of pulmonary alveolar macrophage (PAM) cells. Furthermore, by assessing the major components of OMVs, we confirmed that the DNA of G. parasuis, which is carried by OMVs, is the key component that induces the production of IFN in macrophages. The cGAS–STING–IRF3 pathway links the host’s recognition of G. parasuis OMVs to IFN production. Taken together, our data reveal that G. parasuis OMVs activate cGAS/STING/IRF3 signaling and induce IFN production, which then affects the adhesion and invasion of G. parasuis. The discovery of this vesicle-mediated nucleic acid delivery system redefines the pathogenesis framework for G. parasuis and provides a trans-species conceptual advance in understanding how Gram-negative pathogens exploit vesicular trafficking to manipulate host immunity. |
| format | Article |
| id | doaj-art-c251ad414a254efe8bbd9d965b13a482 |
| institution | DOAJ |
| issn | 1297-9716 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Veterinary Research |
| spelling | doaj-art-c251ad414a254efe8bbd9d965b13a4822025-08-20T03:03:34ZengBMCVeterinary Research1297-97162025-07-0156111310.1186/s13567-025-01553-5Outer membrane vesicles of Glaesserlla parasuis activate the endosomal cGAS–STING–IRF3 pathway through nucleic acid payload delivery: a biological perspective on host defense protocol optimizationKunli Zhang0Zeyi Sun1Xintong Kang2Keda Shi3Pinpin Chu4Dongxia Yang5Zhibiao Bian6Yan Li7Hongchao Gou8Zhiyong Jiang9Nanling Yang10Xia Zhou11Sutian Wang12Zhanyong Wei13Shaolun Zhai14Huahua Kang15Chunling Li16Key Laboratory of Livestock Disease Prevention of Guangdong Province, Guangdong Provincial Observation and Research Station for Animal Disease, Institute of Animal Health, Guangdong Academy of Agricultural SciencesKey Laboratory of Livestock Disease Prevention of Guangdong Province, Guangdong Provincial Observation and Research Station for Animal Disease, Institute of Animal Health, Guangdong Academy of Agricultural SciencesKey Laboratory of Livestock Disease Prevention of Guangdong Province, Guangdong Provincial Observation and Research Station for Animal Disease, Institute of Animal Health, Guangdong Academy of Agricultural SciencesKey Laboratory of Livestock Disease Prevention of Guangdong Province, Guangdong Provincial Observation and Research Station for Animal Disease, Institute of Animal Health, Guangdong Academy of Agricultural SciencesKey Laboratory of Livestock Disease Prevention of Guangdong Province, Guangdong Provincial Observation and Research Station for Animal Disease, Institute of Animal Health, Guangdong Academy of Agricultural SciencesKey Laboratory of Livestock Disease Prevention of Guangdong Province, Guangdong Provincial Observation and Research Station for Animal Disease, Institute of Animal Health, Guangdong Academy of Agricultural SciencesKey Laboratory of Livestock Disease Prevention of Guangdong Province, Guangdong Provincial Observation and Research Station for Animal Disease, Institute of Animal Health, Guangdong Academy of Agricultural SciencesKey Laboratory of Livestock Disease Prevention of Guangdong Province, Guangdong Provincial Observation and Research Station for Animal Disease, Institute of Animal Health, Guangdong Academy of Agricultural SciencesKey Laboratory of Livestock Disease Prevention of Guangdong Province, Guangdong Provincial Observation and Research Station for Animal Disease, Institute of Animal Health, Guangdong Academy of Agricultural SciencesKey Laboratory of Livestock Disease Prevention of Guangdong Province, Guangdong Provincial Observation and Research Station for Animal Disease, Institute of Animal Health, Guangdong Academy of Agricultural SciencesKey Laboratory of Livestock Disease Prevention of Guangdong Province, Guangdong Provincial Observation and Research Station for Animal Disease, Institute of Animal Health, Guangdong Academy of Agricultural SciencesKey Laboratory of Livestock Disease Prevention of Guangdong Province, Guangdong Provincial Observation and Research Station for Animal Disease, Institute of Animal Health, Guangdong Academy of Agricultural SciencesState Key Laboratory of Livestock and Poultry Breeding, Guangdong Key Laboratory of Animal Breeding and Nutrition, Institute of Animal Science, Guangdong Academy of Agricultural SciencesThe College of Animal Science and Veterinary Medicine, Henan Agricultural UniversityKey Laboratory of Livestock Disease Prevention of Guangdong Province, Guangdong Provincial Observation and Research Station for Animal Disease, Institute of Animal Health, Guangdong Academy of Agricultural SciencesKey Laboratory of Livestock Disease Prevention of Guangdong Province, Guangdong Provincial Observation and Research Station for Animal Disease, Institute of Animal Health, Guangdong Academy of Agricultural SciencesKey Laboratory of Livestock Disease Prevention of Guangdong Province, Guangdong Provincial Observation and Research Station for Animal Disease, Institute of Animal Health, Guangdong Academy of Agricultural SciencesAbstract Glaesserlla parasuis (G. parasuis), a Gram-negative pathogen responsible for Glässer's disease, employs outer membrane vesicles (OMVs) as sophisticated nanoscale effectors to modulate host‒pathogen interplay. While bacterial OMVs are recognized as critical mediators of virulence dissemination, their functional orchestration in G. parasuis immunopathogenesis remains unclear. To date, few reports have focused on the relationships among G. parasuis, OMVs and host-susceptible cells; thus, more evidence is urgently needed to explore their crosstalk further. This study revealed a novel immune activation paradigm: both G. parasuis and its OMVs trigger robust type I interferon (IFN) responses via a DNA-sensing cascade. G. parasuis OMVs-Dio were internalized by macrophages in a time-dependent manner, partially via clathrin-mediated endocytosis but mainly via dynamin-dependent endocytosis. Studies have shown that IFNs play key antiviral roles in viral infections and important roles in bacterial infections. Our results suggested that IFNs inhibited G. parasuis adhesion and invasion of pulmonary alveolar macrophage (PAM) cells. Furthermore, by assessing the major components of OMVs, we confirmed that the DNA of G. parasuis, which is carried by OMVs, is the key component that induces the production of IFN in macrophages. The cGAS–STING–IRF3 pathway links the host’s recognition of G. parasuis OMVs to IFN production. Taken together, our data reveal that G. parasuis OMVs activate cGAS/STING/IRF3 signaling and induce IFN production, which then affects the adhesion and invasion of G. parasuis. The discovery of this vesicle-mediated nucleic acid delivery system redefines the pathogenesis framework for G. parasuis and provides a trans-species conceptual advance in understanding how Gram-negative pathogens exploit vesicular trafficking to manipulate host immunity.https://doi.org/10.1186/s13567-025-01553-5Glaesserlla parasuisouter membrane vesiclestype I interferonscGAS–STING |
| spellingShingle | Kunli Zhang Zeyi Sun Xintong Kang Keda Shi Pinpin Chu Dongxia Yang Zhibiao Bian Yan Li Hongchao Gou Zhiyong Jiang Nanling Yang Xia Zhou Sutian Wang Zhanyong Wei Shaolun Zhai Huahua Kang Chunling Li Outer membrane vesicles of Glaesserlla parasuis activate the endosomal cGAS–STING–IRF3 pathway through nucleic acid payload delivery: a biological perspective on host defense protocol optimization Veterinary Research Glaesserlla parasuis outer membrane vesicles type I interferons cGAS–STING |
| title | Outer membrane vesicles of Glaesserlla parasuis activate the endosomal cGAS–STING–IRF3 pathway through nucleic acid payload delivery: a biological perspective on host defense protocol optimization |
| title_full | Outer membrane vesicles of Glaesserlla parasuis activate the endosomal cGAS–STING–IRF3 pathway through nucleic acid payload delivery: a biological perspective on host defense protocol optimization |
| title_fullStr | Outer membrane vesicles of Glaesserlla parasuis activate the endosomal cGAS–STING–IRF3 pathway through nucleic acid payload delivery: a biological perspective on host defense protocol optimization |
| title_full_unstemmed | Outer membrane vesicles of Glaesserlla parasuis activate the endosomal cGAS–STING–IRF3 pathway through nucleic acid payload delivery: a biological perspective on host defense protocol optimization |
| title_short | Outer membrane vesicles of Glaesserlla parasuis activate the endosomal cGAS–STING–IRF3 pathway through nucleic acid payload delivery: a biological perspective on host defense protocol optimization |
| title_sort | outer membrane vesicles of glaesserlla parasuis activate the endosomal cgas sting irf3 pathway through nucleic acid payload delivery a biological perspective on host defense protocol optimization |
| topic | Glaesserlla parasuis outer membrane vesicles type I interferons cGAS–STING |
| url | https://doi.org/10.1186/s13567-025-01553-5 |
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