{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T15:40:46Z","timestamp":1787499646763,"version":"build-2736575974"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"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":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Spinal tuberculosis (STB) and Brucella spondylitis (BS) are the two most common infectious diseases of the spine. Despite overlapping clinical features, their immunopathological mechanisms remain poorly defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed integrated transcriptomic profiling of infected nucleus pulposus tissues from STB and BS patients, combining single-cell RNA sequencing (STB n=3; BS n=3) with bulk RNA sequencing (STB n=7; BS n=5). Single-cell analysis resolved immune heterogeneity and T-cell subset architecture, whereas bulk RNA-seq defined global transcriptional signatures. Cross-platform integration identified concordant differentially expressed genes and shared pathways. AUCell was applied to quantify T-cell functional programmes. Pseudotime trajectory reconstruction, regulon inference, and cell-cell communication analyses were performed to delineate immune circuit differences.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 67,274 high-quality cells were analysed, identifying nine major cell populations, with T cells as a dominant immune component. STB tissues were enriched in inflammatory cells, including monocytes\/macrophages, neutrophils, and osteoclasts, whereas BS showed higher proportions of B and T cells. In STB, CD4 T cells were skewed toward IL26-CD4 T, Cytotoxic CD4 T, Proliferating CD4 T, and Treg subsets, while CD8 T cells were enriched in IFNG-AS1-CD8 T and exhaustion-like populations, reflecting sustained IFN-driven activation with proliferative and apoptotic stress. In contrast, BS exhibited expansion of GZMB-CTLs and IFNG-CTLs subsets, consistent with a focused cytotoxic programme with preserved memory features. Integrated single-cell and bulk analyses demonstrated convergence of overlapping genes on TCR, NF-\u03baB, cytokine signalling, and osteoclast differentiation pathways. Functional scoring and pseudotime analysis indicated broader Th1\/Th17 activation and progression toward terminal exhaustion in STB, whereas BS T cells maintained intermediate effector\u2013memory states. Regulatory network analysis revealed a STAT1\/IRF-dominated interferon axis in STB and an IRF4\/EOMES\/RFX3-centred effector\u2013memory programme in BS. Cell-cell communication mapping showed an MHC-II-CD4 axis predominating in STB and an MHC-I-CD8 axis in BS. Despite divergent immune circuits, both conditions converged on osteoclast differentiation pathways, suggesting immune\u2013bone metabolic coupling as a shared mechanism of vertebral destruction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>STB and BS exhibit pathogen-specific T-cell immune circuits that converge on a common osteo-immune pathway, providing mechanistic insight and potential targets for host-directed therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1811708","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T05:39:41Z","timestamp":1779169181000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Integration of single-cell and bulk RNA sequencing reveals divergent T-cell immune circuits and a shared osteo-immune pathway in spinal tuberculosis and brucellar spondylitis"],"prefix":"10.3389","volume":"16","author":[{"given":"Zongqiang","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Orthopaedic, General Hospital of Ningxia Medical University","place":["Yinchuan, Ningxia Hui Autonomous Region, China"]},{"name":"Ningxia Medical University","place":["Yinchuan, Ningxia Hui Autonomous Region, China"]},{"name":"Research Centre for Prevention and Control of Bone and Joint Tuberculosis, General Hospital of Ningxia Medical University","place":["Yinchuan, Ningxia Hui Autonomous Region, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuefeng","family":"Yue","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic, General Hospital of Ningxia Medical University","place":["Yinchuan, Ningxia Hui Autonomous Region, China"]},{"name":"Ningxia Medical University","place":["Yinchuan, Ningxia Hui Autonomous Region, 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