Role of neutrophils in tuberculosis: A bird's eye view

Abstract

Neutrophils are innate immune cells implicated in the process of killing Mycobacterium tuberculosis early during infection. Once the mycobacteria enter the human system, neutrophils sense and engulf them. By secreting bactericidal enzymes and α-defensins like human neutrophil peptides loaded in their granule armory, neutrophils kill the pathogen. Peripheral blood neutrophils secrete a wide range of cytokines like IL-8, IL-1-β and IFN-γ in response to mycobacterial infection. Thus they signal and activate distant immune cells thereby informing them of prevailing infection. The activated monocytes, dendritic cells and T cells further continue the immune response. As a final call, neutrophils release neutrophil extracellular traps in circulation which can trap mycobacteria in patients with active pulmonary tuberculosis. Extensive neutrophilic response is associated with inflammation, pulmonary destruction, and pathology. For example, inappropriate phagocytosis of mycobacteria-infected neutrophils can damage host cells due to necrosis of neutrophils, leading to chronic inflammation and tissue damage. This dual nature of neutrophils makes them double-edged swords during tuberculosis, and hence data available on neutrophil functions against mycobacterium are controversial and non-uniform. This article reviews the role of neutrophils in tuberculosis infection and highlights research gaps that need to be addressed. We focus on our understanding of new research ideologies targeting neutrophils (a) in the early stages of infection for boosting specific immune functions or (b) in the later stages of infection to prevent inflammatory conditions mediated by activated neutrophils. This would plausibly lead to the development of better tuberculosis vaccines and therapeutics in the future.

Pulmonary MTBVAC vaccination induces immune signatures previously correlated with prevention of tuberculosis infection

“…The effector mechanisms of IL-17A are diverse and can contribute to protection in a number of ways. For example, expression of antimicrobial β-defensin-2 by airway epithelial cells is upregulated after experimental IL-17 treatment, 35 and IL-17A is also known to be involved in neutrophil recruitment to the lungs, which, in turn, has been implied in early protection from TB. 37 , 38 , 39 Additionally, it has been demonstrated that IL-17A is involved in early control of Mtb and formation of protective lymphoid follicles.…”

“…For example, expression of antimicrobial b-defensin-2 by airway epithelial cells is upregulated after experimental IL-17 treatment, 35 and IL-17A is also known to be involved in neutrophil recruitment to the lungs, which, in turn, has been implied in early protection from TB. [36][37][38] Additionally, it has been demonstrated that IL-17A is involved in early control of Mtb and formation of protective lymphoid follicles. 32,39 However, despite evidence of the protective effect of IL-17A in preclinical models, its precise role in human TB remains to be resolved and is likely dependent on factors such as time, location, and magnitude of IL-17A production as well as conditions of comorbidity and coinfection, including HIV.…”

Aggregated Mycobacterium tuberculosis enhances the inflammatory response

“…Neutrophil accumulation in Mtb infection leads to inflammation and has been shown to be detrimental to the host [27,45]. Aggregated Mtb infection led to neutrophil accumulation in a mouse model [11].…”

Independent genomic polymorphisms in the PknH serine threonine kinase locus during evolution of the Mycobacterium tuberculosis Complex affect virulence and host preference

“…bovis infected mice, which also correlates with higher neutrophil infiltration in the total lung cell population. Increased neutrophilia has been previously related to exacerbation of TB pathology and poor prognosis, and a neutrophil-driven IFN-inducible transcript signature in human whole blood of patients with active TB correlates with clinical severity [ 23 , 25 , 26 , 42 ]. Here we show that lung neutrophilia and increased numbers of infected neutrophils in the lung correlate with enhanced pathology, higher bacterial burden and dissemination in M .…”

“…In accordance with the enhanced virulence phenotype of the M. bovis strain, we found a strongly increased neutrophil influx in this group (Fig 2G and 2H). Interestingly, different studies have shown an association, both in humans and animal models, between an increase of neutrophil infiltration in the lungs and a higher degree of TB disease [23][24][25][26].…”