Host-pathogen interactions in tuberculosis: from immunological mechanisms to translational applications

Tuberculosis (TB), which is caused by Mycobacterium tuberculosis (Mtb), remains the leading cause of death from infectious diseases globally. The complexity of host-Mtb interactions poses a fundamental challenge to developing effective prevention and control measures. Recent advances in multi-omics, spatiotemporal biology, and single-cell technologies have yielded transformative insights into Mtb infection dynamics and its intricate crosstalk with the host immune system. In this review, we will first introduce the current knowledge of Mtb-host immunological interplay and discuss it from three interconnected perspectives, including the balance between protective immunity and immunopathology, the coordination between local and systemic immunity, and the contribution of Mtb-induced immune dysregulation to TB comorbidities. We then further highlight translational opportunities via targeting the host-Mtb interface, including predictive biomarkers for Mtb infection and disease progression, next-generation vaccines for immune restoration and TB prevention, and precision strategies to overcome drug resistance and improve treatment outcomes. By integrating the latest discoveries and discussing key unresolved questions, we seek to provide an updated overview of TB pathogenesis with an aim to spur the development of transformative tools for TB control.