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Dual profiling resolves macrophage versus bacterial transcriptional dynamics inside THP-1 macrophages challenged with live or dead intracellular bacteria. Dead Mtb triggers strong immune activation, while live Mtb sustains NF-κB signaling and metabolic reprogramming. Cross-species correlations link Mtb aromatic catabolism to host receptor tyrosine kinase signaling, highlighting pathways tied to persistence versus immune clearance.",{"@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":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/dual-transcriptomic-analysis-unraveling-the-immune-landscape-and-host-pathogen-interactions-during-mycobacterium-tuberculosis-infection-article-summary/432952/",{"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/dual-transcriptomic-analysis-unraveling-the-immune-landscape-and-host-pathogen-interactions-during-mycobacterium-tuberculosis-infection-article-summary/432952.png","ImageObject",300,407,{"name":92,"@type":93},"Blue Pony","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-30","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":14},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What technique does the study use to study host-pathogen interactions in Mtb infection?","Question",{"text":112,"@type":113},"The study applies dual RNA-seq with fluorescent Mtb to simultaneously profile macrophage and bacterial transcriptomes without prior separation of cells.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How do macrophages differ when harboring live versus dead Mtb?",{"text":117,"@type":113},"Macrophages containing dead Mtb show strong immune activation with enhanced antigen presentation and lysosomal function, whereas live Mtb–harboring macrophages display persistent NF-κB signaling and metabolic reprogramming.",{"name":119,"@type":110,"acceptedAnswer":120},"What does cross-species correlation analysis reveal in this work?",{"text":121,"@type":113},"Cross-species correlations identify coordinated transcriptional programs, including a strong inverse association between Mtb aromatic compound catabolism and host receptor tyrosine kinase signaling, alongside links to host lipid transport and steroid biosynthesis.","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},432952,1790764557,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":14,"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},962090760266,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","iScience Article  \nDual transcriptomic analysis unraveling the immune landscape and host-pathogen interactions during Mycobacterium tuberculosis infection  \nAuthors  \nChenyan Shi, Xiaoqian Liu, Dan Chen, ..., Yunlong Hu, Yi Cai, Xinchun Chen  \nCorrespondence  \n[chenxinchun@szu.edu.cn](chenxinchun@szu.edu.cn)  \nIn brief  \nImmunology; Microbiology; Transcriptomics  \n• Lysosomal activation and antigen presentation drive effective macrophage control  \n• Macrophages harboring live Mtb show persistent inflammation and metabolic shift  \n• Cross-species correlations couple host RTK signaling toMtb aromatic catabolism  \nShi et al., 2025, iScience 28, 114102  \nDecember 19, 2025 © 2025 The Author(s) . Published by Elsevier Inc.  \n[https://doi.org/10.1016/j.isci.2025.114102](https://doi.org/10.1016/j.isci.2025.114102)  \nll  \niScience  \nll  \nOPEN ACCESS  \nArticle  \nDual transcriptomic analysis unraveling the immune landscape and host-pathogen interactions  \nduring Mycobacterium tuberculosis infection  \nChenyan Shi,1,2 Xiaoqian Liu,3 Dan Chen,2 Tong Wang,1 Yu Wang,2 Ningjian Cai,2 Zhaodong Li,4 Yunlong Hu,2 Yi Cai,2 and Xinchun Chen2,5,*  \n1School of Public Health, Shenzhen University Medical School, Shenzhen, China  \n2Guangdong Provincial Key Laboratory of Infection Immunity and Inflammation, Department of Pathogen Biology, Shenzhen University Medical School, Shenzhen, China  \n3College of Life Science and Technology, Wuhan Polytechnic University, Wuhan, Hubei, China  \n4Institute of Clinical Medicine, The Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan, China  \n5Lead contact  \n*Correspondence: [chenxinchun@szu.edu.cn](chenxinchun@szu.edu.cn)  \n[https://doi.org/10.1016/j.isci.2025.114102](https://doi.org/10.1016/j.isci.2025.114102)  \nSUMMARY  \nElucidating the host-pathogen interactions is critical for uncovering the mechanisms controlling Mycobacterium tuberculosis (Mtb) infection. Using dual RNA-seq with fluorescent Mtb, we simultaneously profiled macrophage and bacterial transcriptomes to resolve dynamic intracellular responses. Macrophages containing dead Mtb exhibited strong immune activation, including enhanced antigen presentation and lysosomal function, whereas macrophages harboring live Mtb showed persistent NF-κB signaling and metabolic reprogramming. Mtb counteracted host defenses through upregulation of DNA repair genes and manipulation of extracellular matrix signaling via SPP1 and integrins, alongside tryptophan catabolism and lipid binding pathways supporting adaptation. Cross-species correlation analysis revealed coordinated transcriptional programs, notably a strong inverse association between Mtb aromatic compound catabolism and host receptor tyrosine kinase signaling. Additional correlations linked bacterial metabolism with host lipid transport and steroid biosynthesis. Together, these results provide a high resolution view of macrophage and Mtb transcriptional interplay defining bacterial persistence versus immune clearance.  \nINTRODUCTION  \nTuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains one of the most formidable global health challenges, claiming millions of lives each year.1 Central to the pathogenesisofTB is the complex interplay between Mtband the host immune system, particularly the role of macrophages. As the first line of defense, macrophages are tasked with detecting, engulfing, and destroying Mtb upon infection.2 However, the relationship between Mtb and macrophages is dual-faceted.3  \nUnderstanding the molecular basis of this host-pathogen tug-of-war remains a critical goal in TB research, with important implications for the development of host-directed therapies. Dual RNA-seq is a powerful tool that allows the simultaneous, high-precision, and in-depth profiling of both host and pathogen transcriptomes without the need for prior separation. This approach facilitates the examination of temporal shifts in gene expression and helps elucidate how pathogen manipulates ","cbCaiv0BXKKVbWKI","https://ap.wps.com/l/cbCaiv0BXKKVbWKI","pdf",6180775,17,"English","# Summary\n# Introduction\n## Host-pathogen tug-of-war in tuberculosis\n## Why dual RNA-seq enables host and pathogen profiling\n## In vitro infection model and study design","[{\"question\":\"What technique does the study use to study host-pathogen interactions in Mtb infection?\",\"answer\":\"The study applies dual RNA-seq with fluorescent Mtb to simultaneously profile macrophage and bacterial transcriptomes without prior separation of cells.\"},{\"question\":\"How do macrophages differ when harboring live versus dead Mtb?\",\"answer\":\"Macrophages containing dead Mtb show strong immune activation with enhanced antigen presentation and lysosomal function, whereas live Mtb–harboring macrophages display persistent NF-κB signaling and metabolic reprogramming.\"},{\"question\":\"What does cross-species correlation analysis reveal in this work?\",\"answer\":\"Cross-species correlations identify coordinated transcriptional programs, including a strong inverse association between Mtb aromatic compound catabolism and host receptor tyrosine kinase signaling, alongside links to host lipid transport and steroid biosynthesis.\"}]","Dual transcriptomic analysis unraveling the immune landscape and host-pathogen interactions during Mycobacterium tuberculosis infection - Article summary | PDF",1790662070,43]