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This study examined how trained immunity, induced by probiotics and inactivated pathogenic bacterial strains, enhances resistance to Salmonella enterica serovar Typhimurium infection in mice and chickens. Effects were tested in TLR2-deficient mice and assessed using bacterial outer-membrane components, bacterial genome potential, and macrophage-depletion models, emphasizing the cGAS-STING pathway. Results show genome-driven, macrophage-mediated trained immunity with cGAS-STING activation and improved protection.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/trained-immunity-using-probiotics-and-inactivated-pathogens-enhances-resistance-to-salmonella-enterica-serovar-typhimurium-infection-highlights/434397/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/trained-immunity-using-probiotics-and-inactivated-pathogens-enhances-resistance-to-salmonella-enterica-serovar-typhimurium-infection-highlights/434397.png","ImageObject",300,407,{"name":92,"@type":93},"Riley West","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-07","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":46},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What strategy does the study propose to improve resistance to Salmonella Typhimurium?","Question",{"text":112,"@type":113},"It focuses on trained immunity induced by probiotics and inactivated pathogenic bacterial strains as an alternative to antibiotic-based control.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Which immune pathway is emphasized as crucial in trained immunity?",{"text":117,"@type":113},"The cGAS-STING signal pathway is identified as playing a crucial role, with macrophage activation mediating the response.",{"name":119,"@type":110,"acceptedAnswer":120},"How did the study test which bacterial components drive the immune effects?",{"text":121,"@type":113},"It used Toll-like receptor 2-deficient mice to assess whether effects depended on outer membrane components such as peptidoglycan, lipoarabinomannan, and lipoteichoic acid, and found the effects were not dependent on these components while bacterial genomes were significant.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},434397,1790716226,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":46,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},1099523885074,"https://ap-avatar.wpscdn.com/davatar_9964176cb1d06d4a9deccf72a44ae3dc","Journal of Advanced Research 79 (2026) 491–504  \nContents lists available at ScienceDirect  \nJournal of Advanced Research  \njournal [homepage: www. elsevier. com/locate/jare](homepage: www. elsevier. com/locate/jare)  \n| Original Manuscript |  |  |\n| --- | --- | --- |\n| Trained immunity using probiotics and inactivated pathogens enhances resistance to Salmonella enterica serovar Typhimurium infection by activating the cGAS-STING signal pathway in mice and chickens |  | |\n| Junpeng Jia, Wenxin Ji, Ningna Xiong, Jian Lin ⁎, Qian Yang\u003Cbr>MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Wei gang 1, Nanjing, Jiangsu 210095, PR China |  |  |\n| h i g h l i g h t s\u003Cbr>• Trained immunity as a potential alternative to antibiotics for enhancing disease resistance in livestock and poultry.\u003Cbr>• Probiotics and inactivated pathogenic bacterial strains can boost host immunity, providing protection against S. Typhimurium infection.\u003Cbr>• Role of bacterial genomes suggesting their potential as potent immunogens for broad-spectrum immune defense.\u003Cbr>• Macrophages were identified as key players in trained immunity, with cGAS-STING pathway activation enhancing resistance to S. Typhimurium infection.\u003Cbr>• Innovative strategies for disease prevention and control are proposed that leverage macrophage-mediated mechanisms and trained immunity. | g r a p h i c a l a b s t r a c t\u003Cbr>|  |\n\na r t i c l e i n f o  \nArticle history:  \nReceived 11 October 2024 Revised 5 March 2025  \nAccepted 6 March 2025  \nAvailable online 12 March 2025  \nKeywords:  \nTrained immunity S. Typhimurium Bacterial genome Macrophages cGAS-STING pathway  \na b s t r a c t  \nIntroduction: Concerns about antibiotic resistance have prompted interest in alternative strategies for enhancing disease resistance, particularly in livestock and poultry production.  \nObjectives: This study explored the role of trained immunity in enhancing resistance to Salmonella enterica serovar Typhimurium (S. Typhimurium) infection in mice and chickens.  \nMethods: We investigated the effects of probiotics and inactivated pathogenic bacterial strains on host immunity in Toll-like receptor 2-deficient mice (TLR2 −/− ) to assess whether these effects were related to bacterial outer membrane components such as peptidoglycan (PNG), lipoarabinomannan (LAM) and lipoteichoic acid (LTA). Bacterial genomes were evaluated for their ability to enhance the host immune system. Macrophage-depletion models were used to identify the key immune cells involved in trained immunity, with a focus on the cGAS-STING pathway.  \nResults: Probiotics and inactivated pathogenic strains enhanced host immunity and protected against S. Typhimurium infection. As demonstrated in the TLR2-deficient mice, the effects were not dependent on bacterial outer membrane components. Instead, bacterial genomes played a significant role in activating trained immunity. Macrophages were identified as the primary cells that mediated the  \n⁎ Corresponding author at: Nanjing Agricultural University, Weigang 1, Jiangsu, PR China. E-mail address: [linjian@njau.edu.cn](linjian@njau.edu.cn) (J. Lin).  \n[https://doi.org/10.1016/j.jare.2025.03.011](https://doi.org/10.1016/j.jare.2025.03.011)  \n2090-1232/© 2025 The Author(s). Published by Elsevier B.V. on behalf of Cairo University.  \nThis is an open access article under the CC BY-NC-ND license ([http://creativecommons.org/licenses/by-nc-nd/4.0/](http://creativecommons.org/licenses/by-nc-nd/4.0/)).  \nJ. Jia, W. Ji, N. Xiong et al. Journal of Advanced Research 79 (2026) 491–504  \nresponse with the cGAS-STING pathway playing a crucial role. The results observed using the mouse models led to investigating the potential application of trained immunity in poultry.  \nConclusion: Trained immunity activated by probiotics and inactivated bacterial pathogens enhanced resistance against S. Typhimurium infection via macrophage activation ","cbCaicqZKmzSn3UE","https://ap.wps.com/l/cbCaicqZKmzSn3UE","pdf",6521960,14,"English","# Introduction\n# Objectives\n# Methods\n## Toll-like receptor 2-deficient model\n## Bacterial genome evaluation and macrophage depletion\n# Results\n# Conclusion","[{\"question\":\"What strategy does the study propose to improve resistance to Salmonella Typhimurium?\",\"answer\":\"It focuses on trained immunity induced by probiotics and inactivated pathogenic bacterial strains as an alternative to antibiotic-based control.\"},{\"question\":\"Which immune pathway is emphasized as crucial in trained immunity?\",\"answer\":\"The cGAS-STING signal pathway is identified as playing a crucial role, with macrophage activation mediating the response.\"},{\"question\":\"How did the study test which bacterial components drive the immune effects?\",\"answer\":\"It used Toll-like receptor 2-deficient mice to assess whether effects depended on outer membrane components such as peptidoglycan, lipoarabinomannan, and lipoteichoic acid, and found the effects were not dependent on these components while bacterial genomes were significant.\"}]","Trained immunity using probiotics and inactivated pathogens enhances resistance to Salmonella enterica serovar Typhimurium infection - Highlights | PDF",1790669062,35]