期刊
NATURE COMMUNICATIONS
卷 6, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms9451
关键词
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资金
- MRC [U1175.02.002.00014.01]
- Wellcome Trust [081667, 104803, 098316, 097254]
- European Union [PIRSES-GA-2011-295214, FP7 HEALTH-F3-2012-305578]
- National Research Foundation of South Africa [96841]
- MRC [MC_U117565642] Funding Source: UKRI
- Medical Research Council [1105853, MC_U117565642, 1365570] Funding Source: researchfish
- The Francis Crick Institute [10218, 10127, 10219] Funding Source: researchfish
- The Francis Crick Institute
- Cancer Research UK [10126] Funding Source: researchfish
- Wellcome Trust [104803/Z/14/Z] Funding Source: researchfish
Patients with HIV-associated tuberculosis (TB) initiating antiretroviral therapy (ART) may develop immune reconstitution inflammatory syndrome (TB-IRIS). No biomarkers for TB-IRIS have been identified and the underlying mechanisms are unclear. Here we perform transcriptomic profiling of the blood samples of patients with HIV-associated TB. We identify differentially abundant transcripts as early as week 0.5 post ART initiation that predict downstream activation of proinflammatory cytokines in patients who progress to TB-IRIS. At the characteristic time of TB-IRIS onset (week 2), the signature is characterized by over-representation of innate immune mediators including TLR signalling and TREM-1 activation of the inflammasome. In keeping with the transcriptional data, concentrations of plasma cytokines and caspase-1/5 are elevated in TB-IRIS. Inhibition of MyD88 adaptor and group 1 caspases reduces secretion of cytokines including IL-1 in TB-IRIS patients. These data provide insight on the pathogenesis of TB-IRIS and may assist the development of specific therapies.
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