{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:29:55Z","timestamp":1787725795646,"version":"build-2784847793"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"\n Introduction<\/jats:title>\n \n Leishmaniasis is a vector-borne parasitic disease caused by protozoa of the genus\n Leishmania<\/jats:italic>\n , characterized by clinical outcomes ranging from self-limiting cutaneous lesions to fatal visceral disease. Disease progression is multifactorial and is largely shaped by interactions between the parasite and host macrophages, as well as by other host- and pathogen-related factors. Although transcriptomic studies have provided insights into these interactions, differences in experimental design, parasite species, and analytical workflows have limited cross-study comparisons and the identification of conserved molecular responses.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n A systematic review was conducted following PRISMA guidelines to identify publicly available RNA-seq datasets of Leishmania-infected THP-1 macrophages. Raw sequencing data from eligible studies were reanalyzed using a unified bioinformatics pipeline incorporating standardized quality control, differential gene expression analysis, and batch-effect correction to enable robust cross-study integration. Comparative analyses were performed across infection stages and between\n L. infantum<\/jats:italic>\n and\n L. amazonensis<\/jats:italic>\n . The integrated transcriptomic dataset was subsequently used to develop a hypothesis-driven transfer learning framework to evaluate the feasibility of predicting\n L.\u00a0amazonensis<\/jats:italic>\n parasite gene expression at 96 hours post-infection (hpi) from experimentally generated 24 hpi transcriptomic profiles.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Integrated analysis revealed a pronounced early induction of pro-inflammatory and interferon-stimulated genes, including\n CXCL10<\/jats:italic>\n ,\n IL1B<\/jats:italic>\n , and\n IFIT1<\/jats:italic>\n , followed by attenuation of inflammatory signalling at later infection stages. Comparative analyses identified a conserved interferon-driven host response shared between\n L. infantum<\/jats:italic>\n and\n L. amazonensis<\/jats:italic>\n , together with species-specific transcriptional adaptations. The transfer learning framework demonstrated the feasibility of predicting late-stage parasite gene expression from early transcriptomic data, highlighting the potential of machine learning approaches to leverage limited transcriptomic datasets.\n <\/jats:p>\n <\/jats:sec>\n \n Discussion<\/jats:title>\n \n This study provides an integrated transcriptomic framework for investigating host-parasite interactions in\n Leishmania<\/jats:italic>\n -infected macrophages and identifies conserved and species-specific transcriptional responses across infection. Furthermore, the proposed hypothesis-driven transfer learning approach demonstrates the potential to address transcriptomic data scarcity in neglected tropical disease research. Future\n in vitro<\/jats:italic>\n studies and the availability of additional transcriptomic datasets will facilitate improved model training, validation, and generalizability.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1891986","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:01:37Z","timestamp":1787724097000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrative transcriptomics and hypothesis-driven transfer machine learning reveal conserved and species-specific host-parasite dynamics across Leishmania species in THP-1 cells: a systematic review and meta-analysis"],"prefix":"10.3389","volume":"16","author":[{"given":"Hawra","family":"Al-Ghafli","sequence":"first","affiliation":[{"name":"Center for Biosystems and Machines, King Fahd University of Petroleum & Minerals (KFUPM)","place":["Dhahran, Saudi Arabia"]},{"name":"Bioengineering Department, King Fahd University of Petroleum Minerals (KFUPM)","place":["Dhahran, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aymen","family":"Alqurain","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Northern Border University","place":["Rafha, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faisal M.","family":"Alzahrani","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Imam Abdulrahman Bin Faisal University","place":["Dammam, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nasreldin","family":"Elhadi","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Imam Abdulrahman Bin Faisal University","place":["Dammam, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jignesh","family":"Prajapati","sequence":"additional","affiliation":[{"name":"Department of Biochemistry & Forensic Science, University School of Sciences, Gujarat University","place":["Ahmedabad, Gujarat, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haseeb","family":"Nisar","sequence":"additional","affiliation":[{"name":"Center for Finance and Digital Economy, King Fahd University of Petroleum & Minerals (KFUPM)","place":["Dhahran, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0035671","article-title":"Leishmaniasis worldwide and global estimates of its incidence","volume":"7","author":"Alvar","year":"2012","journal-title":"PLoS One"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cimid.2020.101431","article-title":"Serum profile of IL-1\u03b2 and IL-17 cytokines in patients with visceral leishmaniasis","volume":"69","author":"Babaloo","year":"2020","journal-title":"Comp. 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