Cytokines, because of their nature of soluble mediators, represent key elements in mediating and tuning the immune response against Mycobacterium tuberculosis.•Mycobacterium tuberculosis orchestrates the cytokine storm to induce or evade host immune responses.•Granuloma formation is tightly regulated by lung-secreted cytokines.•Perturbation of cytokine signaling represents a critical checkpoint of the immune response against Mycobacterium tuberculosis.•Understanding the balance between pro- and anti-inflammatory cytokines is crucial for developing more effective measures of immune intervention against tuberculosis.