A study published in *Nature* (2010) identifies a blood transcriptional signature in human tuberculosis (TB) driven by interferon (IFN)-inducible neutrophils. The 393-gene signature was found in active TB patients and correlated with disease severity and treatment response. It also showed similarities with some latent TB patients, suggesting subclinical active disease. A 86-gene signature distinguished active TB from other inflammatory and infectious diseases. Pathway analysis revealed that the TB signature was dominated by IFN-γ and Type I IFN αβ signaling. The signature reflected changes in cellular composition and gene expression, and was distinct from other diseases like systemic lupus erythematosus (SLE), which showed increased plasma cell transcripts. The study highlights the role of Type I IFN αβ signaling in TB pathogenesis, with implications for vaccine and therapeutic development. The transcriptional signature could serve as a diagnostic and prognostic tool for TB. The study also showed that the signature diminished after treatment, reflecting radiographic improvement. The findings improve understanding of TB biology and may lead to new diagnostic and therapeutic strategies. The study used whole blood RNA sequencing and flow cytometry to analyze gene expression and cellular composition in TB patients and healthy controls. The results suggest that the TB signature is a reliable biomarker for disease progression and treatment response. The study was conducted in London and South Africa, with participants recruited from hospitals and clinics. The research was supported by the Medical Research Council and the Dana Foundation. The study provides a comprehensive understanding of TB pathogenesis and highlights the importance of IFN signaling in TB. The findings may lead to new diagnostic tools and therapeutic strategies for TB.A study published in *Nature* (2010) identifies a blood transcriptional signature in human tuberculosis (TB) driven by interferon (IFN)-inducible neutrophils. The 393-gene signature was found in active TB patients and correlated with disease severity and treatment response. It also showed similarities with some latent TB patients, suggesting subclinical active disease. A 86-gene signature distinguished active TB from other inflammatory and infectious diseases. Pathway analysis revealed that the TB signature was dominated by IFN-γ and Type I IFN αβ signaling. The signature reflected changes in cellular composition and gene expression, and was distinct from other diseases like systemic lupus erythematosus (SLE), which showed increased plasma cell transcripts. The study highlights the role of Type I IFN αβ signaling in TB pathogenesis, with implications for vaccine and therapeutic development. The transcriptional signature could serve as a diagnostic and prognostic tool for TB. The study also showed that the signature diminished after treatment, reflecting radiographic improvement. The findings improve understanding of TB biology and may lead to new diagnostic and therapeutic strategies. The study used whole blood RNA sequencing and flow cytometry to analyze gene expression and cellular composition in TB patients and healthy controls. The results suggest that the TB signature is a reliable biomarker for disease progression and treatment response. The study was conducted in London and South Africa, with participants recruited from hospitals and clinics. The research was supported by the Medical Research Council and the Dana Foundation. The study provides a comprehensive understanding of TB pathogenesis and highlights the importance of IFN signaling in TB. The findings may lead to new diagnostic tools and therapeutic strategies for TB.