Neutrophils and tuberculosis - insights into immunobiology and pathogenesis

Neutrophils are the most abundant leukocytes in human blood and play a key role in controlling infections. Their high circulating numbers allow rapid recruitment to sites of infection or injury, where they phagocytose pathogens and deploy a multitude of antimicrobial mechanisms. Neutrophil recruitment and clearance regulate infection severity and modulate broader immune response by influencing leukocyte populations. Over the past decade, research has demonstrated that neutrophils are functionally heterogeneous and more complex than previously appreciated with significant implications for immune regulation at sites of infection. Functionally and phenotypically distinct neutrophil subsets have been characterized across infectious, inflammatory and malignant conditions. Numerous studies indicate that neutrophils exert context-dependent protective or pathogenic effects highlighting their more nuanced role during tuberculosis (TB) by conferring early protection but later promoting inflammation, tissue pathology and enhanced bacterial dissemination. Consistent with their protective role, neutrophils not only execute their intrinsic effector functions, but also coordinate immune responses through chemokine and cytokine signaling and potential crosstalk with other immune cells positioning them as key contributors of TB disease progression and outcome. This review summarizes the biology of neutrophil functions with a major emphasis on their role in shaping immune responses during TB infection. We synthesize key findings which highlight their dual, context-dependent function in disease progression. Additionally, we discuss outstanding questions and explore how emerging research in this field may inform strategies to mitigate TB-associated complications.