Airway immune signatures of protection and disease progression in recent human tuberculosis household contacts

We interrogated the airway immune response at single cell resolution in bronchoalveolar lavage (BAL) from PET-CT characterised recent TB household contacts, who either controlled the infection or progressed to TB disease, as well as of active TB patients at diagnosis.

Single cell RNA-sequencing revealed type I IFN-dependent and -independent neutrophil signatures in BAL from active TB patients and TB progressors. We report an inverse relationship between airway neutrophils and T cells, with T cells showing signatures of exhaustion, cytotoxicity and cell death in progressors and active TB patients with a neutrophil dominated airway profile. Conversely, we identified T cell signatures of protection in non-progressor contacts dominated by genes related to regulation, quiescence and a stem-like profile.