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000281912 1001_ $$aTheobald, Sebastian J$$b0
000281912 245__ $$aDeep immune profiling delineates hallmarks of disease heterogeneity in extrapulmonary tuberculosis.
000281912 260__ $$a[London]$$bSpringer Nature$$c2025
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000281912 520__ $$aOur understanding of the immune response in tuberculosis (TB) remains incomplete. This applies in particular to extrapulmonary TB (EPTB), a highly heterogeneous disease affecting up to 30% of patients in certain regions. Based on data-driven clustering of blood transcriptomes in an EPTB patient cohort, we define three highly distinct immunotypes. Combining bulk with single-cell RNA-sequencing delineates immunological trajectories characterized by dynamic IFN- and IL-1-mediated signalling in monocytes, alongside hyperactivation of T and NK cells, ultimately resulting in extensive immune dysregulation. Integrative analysis of multi-omics data provides deep insights into different layers of the anti-tuberculous immune response and the identification of immunotypes enabling stratification strategies for personalized host-directed treatments. In addition, our comprehensive approach helps to develop an accurate diagnostic gene expression signature for both EPTB and pulmonary TB highlighting the translational potential of our data.
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000281912 650_2 $$2MeSH$$aHumans
000281912 650_2 $$2MeSH$$aTuberculosis: immunology
000281912 650_2 $$2MeSH$$aTuberculosis: genetics
000281912 650_2 $$2MeSH$$aTranscriptome
000281912 650_2 $$2MeSH$$aKiller Cells, Natural: immunology
000281912 650_2 $$2MeSH$$aMycobacterium tuberculosis: immunology
000281912 650_2 $$2MeSH$$aSingle-Cell Analysis
000281912 650_2 $$2MeSH$$aMonocytes: immunology
000281912 650_2 $$2MeSH$$aMonocytes: metabolism
000281912 650_2 $$2MeSH$$aGene Expression Profiling
000281912 650_2 $$2MeSH$$aMale
000281912 650_2 $$2MeSH$$aFemale
000281912 650_2 $$2MeSH$$aT-Lymphocytes: immunology
000281912 650_2 $$2MeSH$$aAdult
000281912 650_2 $$2MeSH$$aMiddle Aged
000281912 650_2 $$2MeSH$$aTuberculosis, Pulmonary: immunology
000281912 650_2 $$2MeSH$$aTuberculosis, Pulmonary: genetics
000281912 650_2 $$2MeSH$$aTuberculosis, Extrapulmonary
000281912 7001_ $$0P:(DE-2719)9001875$$aDahm, Kilian$$b1$$eFirst author
000281912 7001_ $$00000-0002-2933-2143$$aLange, Dinah$$b2
000281912 7001_ $$0P:(DE-2719)9001907$$aSpintge, Jannis Sebastian$$b3$$udzne
000281912 7001_ $$aWinter, Sandra$$b4
000281912 7001_ $$aKlingmüller, Angela$$b5
000281912 7001_ $$0P:(DE-2719)9001067$$aHolsten, Lisa$$b6
000281912 7001_ $$00000-0003-2945-9897$$aSimonis, Alexander$$b7
000281912 7001_ $$0P:(DE-2719)9000846$$aDe Domenico, Elena$$b8
000281912 7001_ $$00000-0002-6312-4591$$aWalczak, Henning$$b9
000281912 7001_ $$0P:(DE-2719)9002579$$avan Uelft, Martina$$b10$$udzne
000281912 7001_ $$0P:(DE-2719)2811660$$aSchultze, Joachim L$$b11
000281912 7001_ $$0P:(DE-2719)2812219$$aBeyer, Marc D$$b12
000281912 7001_ $$0P:(DE-2719)9000845$$aUlas, Thomas$$b13$$eLast author$$udzne
000281912 7001_ $$aSuárez, Isabelle$$b14
000281912 7001_ $$00000-0001-8351-2690$$aRybniker, Jan$$b15
000281912 773__ $$0PERI:(DE-600)2553671-0$$a10.1038/s41467-025-65561-x$$gVol. 16, no. 1, p. 9662$$n1$$p9662$$tNature Communications$$v16$$x2041-1723$$y2025
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