{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T05:43:20Z","timestamp":1789191800212,"version":"build-2803163510"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T00:00:00Z","timestamp":1749081600000},"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. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p><jats:italic>Brucella<\/jats:italic> spp., facultative intracellular pathogens that cause brucellosis, drive pathogenesis by invading host cells and establishing intracellular persistence. While their molecular mechanisms are well-characterized, how <jats:italic>Brucella<\/jats:italic> induces chromatin restructuring in host cells remains poorly understood, representing a critical gap in host-pathogen interaction research.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using an established <jats:italic>in vitro<\/jats:italic> infection model of <jats:italic>Brucella<\/jats:italic>-infected RAW264.7 murine macrophages, we integrated Hi-C, ATAC-seq, and RNA-seq to generate multi-omics datasets. Multidimensional comparative genomics approaches were employed to systematically map infection-induced changes in host chromatin architecture and functional genomic organization.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our findings unveiled substantial alterations in the host chromatin architecture, characterized by a reduction in B-B compartment regions interactions, an increase in A-B compartment interactions, and diminished long-range chromatin contacts. Crucially, <jats:italic>Brucella<\/jats:italic> reshaped chromatin compartmentalization, activating interferon-stimulated genes (ISGs) in regions transitioning from compartment B to A. Enhanced sub-TADs interactions within ISG clusters further facilitated their coordinated expression. Additionally, infection remodeled chromatin loop structures, strengthening interactions linked to immune-related gene activation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These results demonstrate that host cells undergo substantial chromatin remodeling during acute <jats:italic>Brucella<\/jats:italic> infection as a defense mechanism against pathogen invasion. Our findings provide critical insights into host-pathogen interactions and suggest potential epigenetic targets for managing brucellosis.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1574006","type":"journal-article","created":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T05:28:24Z","timestamp":1749101304000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Brucella infection induces chromatin restructuring in host cells to activate immune 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