An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis

摘要: Tuberculosis (TB), caused by infection with Mycobacterium tuberculosis, is a major cause of morbidity and mortality worldwide. Efforts to control it are hampered difficulties diagnosis, prevention treatment. Most people infected M. tuberculosis remain asymptomatic, termed latent TB, 10% lifetime risk developing active TB disease. Current tests, however, cannot identify which individuals will develop The immune response complex incompletely characterized, hindering development new diagnostics, therapies vaccines. Here we whole-blood 393 transcript signature for in intermediate high-burden settings, correlating radiological extent disease reverting that healthy controls after A subset patients had signatures similar those TB. We also specific 86-transcript discriminates from other inflammatory infectious diseases. Modular pathway analysis revealed the was dominated neutrophil-driven interferon (IFN)-inducible gene profile, consisting both IFN-gamma type I IFN-alphabeta signalling. Comparison transcriptional purified cells flow cytometric suggest this reflects changes cellular composition altered expression. Although an IFN-inducible observed whole blood systemic lupus erythematosus (SLE), their complete modular differed increased abundance plasma cell transcripts. Our studies demonstrate hitherto underappreciated role signalling pathogenesis has implications vaccine therapeutic development. study provides broad range biomarkers potential as diagnostic prognostic tools combat epidemic.