Neutrophils from Protection to Pathogenesis in Tuberculosis

Mycobacterium tuberculosis ( Mtb ), the etiological agent of tuberculosis (TB), is well-equipped to establish infection, endure host immune pressures, and propagate to naïve individuals; its success depends on its ability to actively evade and recalibrate the host immune system. The balance between immunological control and bacterial persistence often shapes the clinical outcome of an Mtb infection. While the roles of macrophages and T cells have been extensively characterized in this balance, the contribution of neutrophils remains comparatively underexplored. The abundance of neutrophils in TB granulomas and their correlation with disease severity in humans and animal models suggest a vital role for these immune cells in TB infection. This review summarizes our current understanding of neutrophils in TB pathogenesis at different scales and models─in vitro, ex vivo, and in vivo─while highlighting some of the outstanding questions at each level. We delve into emerging concepts in neutrophil biology, including heterogeneity, metabolism, and maturation, along with Mtb 's mechanisms to modulate and evade neutrophil bactericidal stresses to ensure its persistence. A deeper understanding of neutrophil biology and the interaction with Mtb could inform the development of more effective therapies and diagnostic strategies against TB.