As one of the most common mycotoxins, deoxynivalenol (DON) can contaminate a wide range of crops and foods. Porcine circovirus 2 (PCV2) is a kind of immunosuppressive virus, which can cause porcine circovirus associated disease (PCVD) in pig farms infected with PCV2. Pigs are extremely sensitive to DON, and PCV2-infected pig farms are often contaminated with DON. Our previous studies indicated that Bacillus amyloliquefaciens B10 (B10) has the potential to alleviate the toxicity of mycotoxins. The research was aimed at investigating the effects of Bacillus amyloliquefaciens B10 on the immunosuppressive effects caused by both DON and PCV2 infection. The results indicated that the expression of the PCV2 capsid protein CAP was significantly decreased after pretreatment with Bacillus amyloliquefaciens B10. Then, the effects of the Bacillus amyloliquefaciens B10 pretreatment on the type I interferon, antiviral protein and the antiviral signal pathway cGAS-STING was further investigated. The findings displayed that the expression of the type I interferon and antiviral protein were increased, while the IL-10 were decreased after pretreatment with Bacillus amyloliquefaciens B10. The inhibition of DON on the cGAS-STING signal pathway was relieved. Furthermore, it was found that this intervention effect was produced by inhibiting autophagy. In summary, Bacillus amyloliquefaciens B10 can mitigate the immunosuppressive effects of PCV2 and DON by inhibiting the production of autophagy.

College of Life Science Yangtze University Jingzhou 434025 China

Department of Chemistry Faculty of Science University of Hradec Kralove 50003 Hradec Kralove Czech Republic

Joint Research Center for Foodborne Functional Factors and Green Preparation School of Food and Biological Engineering Engineering Research Center of Bio Process Ministry of Education Hefei University of Technology Hefei 230009 China

Key Laboratory of Zoonosis of Liaoning Province College of Animal Science and Veterinary Medicine Shenyang Agricultural University Shenyang 110866 China

MOE Joint International Research Laboratory of Animal Health and Food Safety College of Veterinary Medicine Nanjing Agricultural University Nanjing 210095 China

Zobrazit více v PubMed

Sun Y., Jiang J., Mu P., Lin R., Wen J., Deng Y. Toxicokinetics and Metabolism of Deoxynivalenol in Animals and Humans. Arch. Toxicol. 2022;96:2639–2654. doi: 10.1007/s00204-022-03337-8. PubMed DOI

You L., Zhao Y., Kuca K., Wang X., Oleksak P., Chrienova Z., Nepovimova E., Jaćević V., Wu Q., Wu W. Hypoxia, Oxidative Stress, and Immune Evasion: A Trinity of the Trichothecenes T-2 Toxin and Deoxynivalenol (DON) Arch. Toxicol. 2021;95:1899–1915. doi: 10.1007/s00204-021-03030-2. PubMed DOI

Lei R., Jiang N., Zhang Q., Hu S., Dennis B.S., He S., Guo X. Prevalence of Selenium, T-2 Toxin, and Deoxynivalenol in Kashin-Beck Disease Areas in Qinghai Province, Northwest China. Biol. Trace Elem. Res. 2016;171:34–40. doi: 10.1007/s12011-015-0495-0. PubMed DOI

Zhai S.-L., Lu S.-S., Wei W.-K., Lv D.-H., Wen X.-H., Zhai Q., Chen Q.-L., Sun Y.-W., Xi Y. Reservoirs of Porcine Circoviruses: A Mini Review. Front. Vet. Sci. 2019;6:319. doi: 10.3389/fvets.2019.00319. PubMed DOI PMC

Opriessnig T., Meng X.-J., Halbur P.G. Porcine Circovirus Type 2 Associated Disease: Update on Current Terminology, Clinical Manifestations, Pathogenesis, Diagnosis, and Intervention Strategies. J. Vet. Diagn. Investig. 2007;19:591–615. doi: 10.1177/104063870701900601. PubMed DOI

Sanchez R.E., Meerts P., Nauwynck H.J., Ellis J.A., Pensaert M.B. Characteristics of Porcine Circovirus-2 Replication in Lymphoid Organs of Pigs Inoculated in Late Gestation or Postnatally and Possible Relation to Clinical and Pathological Outcome of Infection. J. Vet. Diagn. Investig. 2004;16:175–185. doi: 10.1177/104063870401600301. PubMed DOI

Sewalt V., Shanahan D., Gregg L., La Marta J., Carrillo R. The Generally Recognized as Safe (GRAS) Process for Industrial Microbial Enzymes. Ind. Biotechnol. 2016;12:295–302. doi: 10.1089/ind.2016.0011. DOI

Abriouel H., Franz C.M.A.P., Ben Omar N., Gálvez A. Diversity and Applications of Bacillus Bacteriocins. FEMS Microbiol. Rev. 2011;35:201–232. doi: 10.1111/j.1574-6976.2010.00244.x. PubMed DOI

WoldemariamYohannes K., Wan Z., Yu Q., Li H., Wei X., Liu Y., Wang J., Sun B. Prebiotic, Probiotic, Antimicrobial, and Functional Food Applications of Bacillus amyloliquefaciens. J. Agric. Food Chem. 2020;68:14709–14727. doi: 10.1021/acs.jafc.0c06396. PubMed DOI

Chen Y.-C., Huang S.-D., Tu J.-H., Yu J.-S., Nurlatifah A.O., Chiu W.-C., Su Y.-H., Chang H.-L., Putri D.A., Cheng H.-L. Exopolysaccharides of Modulate Glycemic Level in Mice and Promote Glucose Uptake of Cells through the Activation of Akt. Int. J. Biol. Macromol. 2020;146:202–211. doi: 10.1016/j.ijbiomac.2019.12.217. PubMed DOI

Chang X., Wu Z., Wu S., Dai Y., Sun C. Degradation of Ochratoxin A by Bacillus amyloliquefaciens ASAG1. Food Addit. Contam. Part A Chem. Anal. Control Expo. Risk Assess. 2015;32:564–571. doi: 10.1080/19440049.2014.991948. PubMed DOI

Siahmoshteh F., Siciliano I., Banani H., Hamidi-Esfahani Z., Razzaghi-Abyaneh M., Gullino M.L., Spadaro D. Efficacy of Bacillus Subtilis and Bacillus amyloliquefaciens in the Control of Aspergillus Parasiticus Growth and Aflatoxins Production on Pistachio. Int. J. Food Microbiol. 2017;254:47–53. doi: 10.1016/j.ijfoodmicro.2017.05.011. PubMed DOI

Xu J., Wang H., Zhu Z., Ji F., Yin X., Hong Q., Shi J. Isolation and Characterization of Bacillus amyloliquefaciens ZDS-1: Exploring the Degradation of Zearalenone by Bacillus spp. Food Control. 2016;68:244–250. doi: 10.1016/j.foodcont.2016.03.030. DOI

Zhao Y., Wang T., Li P., Chen J., Nepovimova E., Long M., Wu W., Kuca K. Bacillus amyloliquefaciens B10 Can Alleviate Aflatoxin B1-Induced Kidney Oxidative Stress and Apoptosis in Mice. Ecotoxicol. Environ. Saf. 2021;218:112286. doi: 10.1016/j.ecoenv.2021.112286. PubMed DOI

Li X., Lv Z., Chen J., Nepovimova E., Long M., Wu W., Kuca K. Bacillus amyloliquefaciens B10 Can Alleviate Liver Apoptosis and Oxidative Stress Induced by Aflatoxin B1. Food Chem. Toxicol. 2021;151:112124. doi: 10.1016/j.fct.2021.112124. PubMed DOI

Chen J., Lv Z., Cheng Z., Wang T., Li P., Wu A., Nepovimova E., Long M., Wu W., Kuca K. Bacillus amyloliquefaciens B10 Inhibits Aflatoxin B1-Induced Cecal Inflammation in Mice by Regulating Their Intestinal Flora. Food Chem. Toxicol. 2021;156:112438. doi: 10.1016/j.fct.2021.112438. PubMed DOI

Wu J., Sun L., Chen X., Du F., Shi H., Chen C., Chen Z.J. Cyclic GMP-AMP Is an Endogenous Second Messenger in Innate Immune Signaling by Cytosolic DNA. Science. 2013;339:826–830. doi: 10.1126/science.1229963. PubMed DOI PMC

Decout A., Katz J.D., Venkatraman S., Ablasser A. The cGAS-STING Pathway as a Therapeutic Target in Inflammatory Diseases. Nat. Rev. Immunol. 2021;21:548–569. doi: 10.1038/s41577-021-00524-z. PubMed DOI PMC

Paul P., Münz C. Autophagy and Mammalian Viruses: Roles in Immune Response, Viral Replication, and Beyond. Adv. Virus Res. 2016;95:149–195. doi: 10.1016/bs.aivir.2016.02.002. PubMed DOI

Nassour J., Radford R., Correia A., Fusté J.M., Schoell B., Jauch A., Shaw R.J., Karlseder J. Autophagic Cell Death Restricts Chromosomal Instability during Replicative Crisis. Nature. 2019;565:659–663. doi: 10.1038/s41586-019-0885-0. PubMed DOI PMC

Liu Z., Wang M., Wang X., Bu Q., Wang Q., Su W., Li L., Zhou H., Lu L. XBP1 Deficiency Promotes Hepatocyte Pyroptosis by Impairing Mitophagy to Activate mtDNA-cGAS-STING Signaling in Macrophages during Acute Liver Injury. Redox Biol. 2022;52:102305. doi: 10.1016/j.redox.2022.102305. PubMed DOI PMC

Grau-Roma L., Stockmarr A., Kristensen C.S., Enøe C., López-Soria S., Nofrarías M., Bille-Hansen V., Hjulsager C.K., Sibila M., Jorsal S.E., et al. Infectious Risk Factors for Individual Postweaning Multisystemic Wasting Syndrome (PMWS) Development in Pigs from Affected Farms in Spain and Denmark. Res. Vet. Sci. 2012;93:1231–1240. doi: 10.1016/j.rvsc.2012.07.001. PubMed DOI

Milićević D., Nastasijevic I., Petrovic Z. Mycotoxin in the Food Supply Chain-Implications for Public Health Program. J. Environ. Sci. Health C Environ. Carcinog. Ecotoxicol. Rev. 2016;34:293–319. doi: 10.1080/10590501.2016.1236607. PubMed DOI

Savard C., Provost C., Alvarez F., Pinilla V., Music N., Jacques M., Gagnon C.A., Chorfi Y. Effect of Deoxynivalenol (DON) Mycotoxin on in Vivo and in Vitro Porcine Circovirus Type 2 Infections. Vet. Microbiol. 2015;176:257–267. doi: 10.1016/j.vetmic.2015.02.004. PubMed DOI

Savard C., Pinilla V., Provost C., Gagnon C.A., Chorfi Y. In Vivo Effect of Deoxynivalenol (DON) Naturally Contaminated Feed on Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Infection. Vet. Microbiol. 2014;174:419–426. doi: 10.1016/j.vetmic.2014.10.019. PubMed DOI

Liu J.-T., Lumsden J.S. Impact of Feed Restriction, Chloroquine and Deoxynivalenol on Viral Haemorrhagic Septicaemia Virus IVb in Fathead Minnow Pimephales Promelas Rafinesque. J. Fish Dis. 2021;44:217–220. doi: 10.1111/jfd.13300. PubMed DOI

Poelaert K.C.K., Van Cleemput J., Laval K., Favoreel H.W., Couck L., Van den Broeck W., Azab W., Nauwynck H.J. Equine Herpesvirus 1 Bridles T Lymphocytes To Reach Its Target Organs. J. Virol. 2019;93:e02098-18. doi: 10.1128/JVI.02098-18. PubMed DOI PMC

Li M., Harkema J.R., Cuff C.F., Pestka J.J. Deoxynivalenol Exacerbates Viral Bronchopneumonia Induced by Respiratory Reovirus Infection. Toxicol. Sci. 2007;95:412–426. doi: 10.1093/toxsci/kfl153. PubMed DOI

Liu D., Ge L., Wang Q., Su J., Chen X., Wang C., Huang K. Low-Level Contamination of Deoxynivalenol: A Threat from Environmental Toxins to Porcine Epidemic Diarrhea Virus Infection. Environ. Int. 2020;143:105949. doi: 10.1016/j.envint.2020.105949. PubMed DOI PMC

Li X., Wang Q., Hu X., Liu W. Current Status of Probiotics as Supplements in the Prevention and Treatment of Infectious Diseases. Front. Cell. Infect. Microbiol. 2022;12:789063. doi: 10.3389/fcimb.2022.789063. PubMed DOI PMC

Rastelli M., Cani P.D., Knauf C. The Gut Microbiome Influences Host Endocrine Functions. Endocr. Rev. 2019;40:1271–1284. doi: 10.1210/er.2018-00280. PubMed DOI

Zeng Z., Zhou Y., Xu Y., Wang S., Wang B., Zeng Z., Wang Q., Ye X., Jin L., Yue M., et al. Bacillus amyloliquefaciens SC06 Alleviates the Obesity of Ob/Ob Mice and Improves Their Intestinal Microbiota and Bile Acid Metabolism. Food Funct. 2022;13:5381–5395. doi: 10.1039/D1FO03170H. PubMed DOI

Jebali R., Ben Salah-Abbès J., Abbès S., Hassan A.M., Abdel-Aziem S.H., El-Nekeety A.A., Oueslati R., Abdel-Wahhab M.A. Lactobacillus Plantarum Alleviate Aflatoxins (B1 and M1) Induced Disturbances in the Intestinal Genes Expression and DNA Fragmentation in Mice. Toxicon. 2018;146:13–23. doi: 10.1016/j.toxicon.2018.03.008. PubMed DOI

Falcinelli S., Rodiles A., Hatef A., Picchietti S., Cossignani L., Merrifield D.L., Unniappan S., Carnevali O. Influence of Probiotics Administration on Gut Microbiota Core: A Review on the Effects on Appetite Control, Glucose, and Lipid Metabolism. J. Clin. Gastroenterol. 2018;52((Suppl. S1)):S50–S56. doi: 10.1097/MCG.0000000000001064. PubMed DOI

Dimidi E., Christodoulides S., Scott S.M., Whelan K. Mechanisms of Action of Probiotics and the Gastrointestinal Microbiota on Gut Motility and Constipation. Adv. Nutr. 2017;8:484–494. doi: 10.3945/an.116.014407. PubMed DOI PMC

Lee A.J., Ashkar A.A. The Dual Nature of Type I and Type II Interferons. Front. Immunol. 2018;9:2061. doi: 10.3389/fimmu.2018.02061. PubMed DOI PMC

Jiao R., Cai Y., He P., Munir S., Li X., Wu Y., Wang J., Xia M., He P., Wang G., et al. Bacillus amyloliquefaciens YN201732 Produces Lipopeptides With Promising Biocontrol Activity Against Fungal Pathogen Erysiphe Cichoracearum. Front. Cell. Infect. Microbiol. 2021;11:598999. doi: 10.3389/fcimb.2021.598999. PubMed DOI PMC

Ma Z., Jacobs S.R., West J.A., Stopford C., Zhang Z., Davis Z., Barber G.N., Glaunsinger B.A., Dittmer D.P., Damania B. Modulation of the cGAS-STING DNA Sensing Pathway by Gammaherpesviruses. Proc. Natl. Acad. Sci. USA. 2015;112:E4306–E4315. doi: 10.1073/pnas.1503831112. PubMed DOI PMC

Lio C.-W.J., McDonald B., Takahashi M., Dhanwani R., Sharma N., Huang J., Pham E., Benedict C.A., Sharma S. cGAS-STING Signaling Regulates Initial Innate Control of Cytomegalovirus Infection. J. Virol. 2016;90:7789–7797. doi: 10.1128/JVI.01040-16. PubMed DOI PMC

Wu J., Li W., Shao Y., Avey D., Fu B., Gillen J., Hand T., Ma S., Liu X., Miley W., et al. Inhibition of cGAS DNA Sensing by a Herpesvirus Virion Protein. Cell Host Microbe. 2015;18:333–344. doi: 10.1016/j.chom.2015.07.015. PubMed DOI PMC

Gan F., Zhou Y., Qian G., Huang D., Hou L., Liu D., Chen X., Wang T., Jiang P., Lei X., et al. PCV2 Infection Aggravates Ochratoxin A-Induced Nephrotoxicity via Autophagy Involving P38 Signaling Pathway in Vivo and in Vitro. Environ. Pollut. 2018;238:656–662. doi: 10.1016/j.envpol.2018.03.032. PubMed DOI

Liu D., Lin J., Su J., Chen X., Jiang P., Huang K. Glutamine Deficiency Promotes PCV2 Infection through Induction of Autophagy via Activation of ROS-Mediated JAK2/STAT3 Signaling Pathway. J. Agric. Food Chem. 2018;66:11757–11766. doi: 10.1021/acs.jafc.8b04704. PubMed DOI

Liu D., Xu J., Qian G., Hamid M., Gan F., Chen X., Huang K. Selenizing Astragalus Polysaccharide Attenuates PCV2 Replication Promotion Caused by Oxidative Stress through Autophagy Inhibition via PI3K/AKT Activation. Int. J. Biol. Macromol. 2018;108:350–359. doi: 10.1016/j.ijbiomac.2017.12.010. PubMed DOI

Bao C.L., Liu S.Z., Shang Z.D., Liu Y.J., Wang J., Zhang W.X., Dong B., Cao Y.H. Bacillus amyloliquefaciens TL106 Protects Mice against Enterohaemorrhagic Escherichia Coli O157:H7-Induced Intestinal Disease through Improving Immune Response, Intestinal Barrier Function and Gut Microbiota. J. Appl. Microbiol. 2021;131:470–484. doi: 10.1111/jam.14952. PubMed DOI