Lactiplantibacillus plantarum extracellular vesicles exert anti-PEDV effects through STING-dependent autophagy

Abstract Porcine epidemic diarrhea virus (PEDV) infection causes severe gastrointestinal and lethal disease in piglets, leading to huge economic losses for the swine industry worldwide. Recent studies have emphasized probiotics can regulate innate immunity and cellular functions through interaction...

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Main Authors: Shihan Zhang, Xin Shan, Guanglong Qu, Anqi Sun, Junhong Xing, Qiuyuan Liu, Zixuan Liu, Yibing Wang, Xinyue Zhang, Xin Cao, Yan Zeng, Jianzhong Wang, Chunfeng Wang, Jingtao Hu
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Language:English
Published: BMC 2025-05-01
Series:BMC Microbiology
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Online Access:https://doi.org/10.1186/s12866-025-04019-y
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author Shihan Zhang
Xin Shan
Guanglong Qu
Anqi Sun
Junhong Xing
Qiuyuan Liu
Zixuan Liu
Yibing Wang
Xinyue Zhang
Xin Cao
Yan Zeng
Jianzhong Wang
Chunfeng Wang
Jingtao Hu
author_facet Shihan Zhang
Xin Shan
Guanglong Qu
Anqi Sun
Junhong Xing
Qiuyuan Liu
Zixuan Liu
Yibing Wang
Xinyue Zhang
Xin Cao
Yan Zeng
Jianzhong Wang
Chunfeng Wang
Jingtao Hu
author_sort Shihan Zhang
collection DOAJ
description Abstract Porcine epidemic diarrhea virus (PEDV) infection causes severe gastrointestinal and lethal disease in piglets, leading to huge economic losses for the swine industry worldwide. Recent studies have emphasized probiotics can regulate innate immunity and cellular functions through interaction with intestinal epithelial cells via extracellular vesicles (EVs) as effective carriers. The cGAS-STING signaling pathway is crucial for inducing type I interferons (IFNs) to establish antiviral innate immunity. It also triggers cellular autophagy, which helps maintain intracellular environmental homeostasis. In our study, we found that Lactiplantibacillus plantarum extracellular vesicles (LpEVs) significantly activated the cGAS-STING signaling pathway in porcine intestinal epithelial cells (IPEC-J2), thereby enhancing antiviral immune responses. Notably, compared to the untreated control group, 10 μg/mL LpEVs retained the capacity to activate the cGAS-STING pathway, but their activation efficacy was significantly lower than that of 2.5 μg/mL, suggesting a potential feedback regulatory mechanism at higher concentrations. Furthermore, 10 μg/mL LpEVs regulated cGAS-STING activation through autophagy induction, and this autophagic response was STING-dependent. Additionally, LpEVs at concentrations of 2.5, 5, and 10 μg/mL all significantly inhibited the proliferation of PEDV. However, 10 μg/mL LpEVs exhibited a stronger inhibitory effect on PEDV replication compared to 2.5 or 5 μg/mL doses, and this enhanced antiviral activity was closely associated with autophagy. Our findings elucidate the underlying mechanism of antiviral effects of probiotics through regulating innate immunity and autophagy, which highlights the critical role of LpEVs in preventing PEDV infection as a potential antiviral agent.
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publisher BMC
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spelling doaj-art-b0fdd57df6b745c7acd0184bd3f3eb172025-08-20T03:09:35ZengBMCBMC Microbiology1471-21802025-05-0125111410.1186/s12866-025-04019-yLactiplantibacillus plantarum extracellular vesicles exert anti-PEDV effects through STING-dependent autophagyShihan Zhang0Xin Shan1Guanglong Qu2Anqi Sun3Junhong Xing4Qiuyuan Liu5Zixuan Liu6Yibing Wang7Xinyue Zhang8Xin Cao9Yan Zeng10Jianzhong Wang11Chunfeng Wang12Jingtao Hu13Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of EducationEngineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of EducationEngineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of EducationEngineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of EducationEngineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of EducationCollege of Animal Science and Technology, Jilin Agricultural UniversityAnimal Medical College, Jilin Agricultural UniversityAnimal Medical College, Jilin Agricultural UniversityEngineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of EducationEngineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of EducationEngineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of EducationEngineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of EducationEngineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of EducationEngineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of EducationAbstract Porcine epidemic diarrhea virus (PEDV) infection causes severe gastrointestinal and lethal disease in piglets, leading to huge economic losses for the swine industry worldwide. Recent studies have emphasized probiotics can regulate innate immunity and cellular functions through interaction with intestinal epithelial cells via extracellular vesicles (EVs) as effective carriers. The cGAS-STING signaling pathway is crucial for inducing type I interferons (IFNs) to establish antiviral innate immunity. It also triggers cellular autophagy, which helps maintain intracellular environmental homeostasis. In our study, we found that Lactiplantibacillus plantarum extracellular vesicles (LpEVs) significantly activated the cGAS-STING signaling pathway in porcine intestinal epithelial cells (IPEC-J2), thereby enhancing antiviral immune responses. Notably, compared to the untreated control group, 10 μg/mL LpEVs retained the capacity to activate the cGAS-STING pathway, but their activation efficacy was significantly lower than that of 2.5 μg/mL, suggesting a potential feedback regulatory mechanism at higher concentrations. Furthermore, 10 μg/mL LpEVs regulated cGAS-STING activation through autophagy induction, and this autophagic response was STING-dependent. Additionally, LpEVs at concentrations of 2.5, 5, and 10 μg/mL all significantly inhibited the proliferation of PEDV. However, 10 μg/mL LpEVs exhibited a stronger inhibitory effect on PEDV replication compared to 2.5 or 5 μg/mL doses, and this enhanced antiviral activity was closely associated with autophagy. Our findings elucidate the underlying mechanism of antiviral effects of probiotics through regulating innate immunity and autophagy, which highlights the critical role of LpEVs in preventing PEDV infection as a potential antiviral agent.https://doi.org/10.1186/s12866-025-04019-yLactiplantibacillus plantarumExtracellular vesiclesAutophagySTINGPEDV
spellingShingle Shihan Zhang
Xin Shan
Guanglong Qu
Anqi Sun
Junhong Xing
Qiuyuan Liu
Zixuan Liu
Yibing Wang
Xinyue Zhang
Xin Cao
Yan Zeng
Jianzhong Wang
Chunfeng Wang
Jingtao Hu
Lactiplantibacillus plantarum extracellular vesicles exert anti-PEDV effects through STING-dependent autophagy
BMC Microbiology
Lactiplantibacillus plantarum
Extracellular vesicles
Autophagy
STING
PEDV
title Lactiplantibacillus plantarum extracellular vesicles exert anti-PEDV effects through STING-dependent autophagy
title_full Lactiplantibacillus plantarum extracellular vesicles exert anti-PEDV effects through STING-dependent autophagy
title_fullStr Lactiplantibacillus plantarum extracellular vesicles exert anti-PEDV effects through STING-dependent autophagy
title_full_unstemmed Lactiplantibacillus plantarum extracellular vesicles exert anti-PEDV effects through STING-dependent autophagy
title_short Lactiplantibacillus plantarum extracellular vesicles exert anti-PEDV effects through STING-dependent autophagy
title_sort lactiplantibacillus plantarum extracellular vesicles exert anti pedv effects through sting dependent autophagy
topic Lactiplantibacillus plantarum
Extracellular vesicles
Autophagy
STING
PEDV
url https://doi.org/10.1186/s12866-025-04019-y
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