Susceptibility to Tuberculosis Is Associated With PI3K-Dependent Increased Mobilization of Neutrophils

Neutrophilia is a condition commonly observed in patients with late-stage tuberculosis, but evidence suggests that increased neutrophil influx begins early after infection in susceptible hosts and functions to promote a nutrient-replete niche that promotes Mycobacterium tuberculosis survival and persistence. As the disease progresses, an increase in the number of neutrophil-like cells is observed, all of which exhibit characteristics associated with (i) phenotypic and biochemical features of immaturity, (ii) the inability to activate T-cells, (iii) hyper-inflammation, and (iv) prolonged survival. Transcriptomics reveal a common set of molecules associated with the PI3–Kinase pathway that are dysregulated in patients with active tuberculosis. Closer inspection of their individual biological roles reveal their ability to modulate the IL-17/G–CSF axis, induce leukocyte receptor activation, and regulate apoptosis and motility. This review draws attention to neutrophil hyper-reactivity as a driving force for both the establishment and progression of tuberculosis disease in susceptible individuals.