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.

Keywords: Neutrophils; apoptosis; immune response; macrophages; phagocytosis; tuberculosis.

Figure 1.

Once M. tuberculosis enters the human system, neutrophils recognize the pathogen and phagocytose it. A cascade of events then starts: in direct killing, neutrophils release lysosomal enzymes, human neutrophil peptides, reactive oxygen species, etc, which directly lyse the mycobacterium. Another mechanism is also activated during the apoptotic phase of neutrophils, wherein they release neutrophil extracellular traps, which can trap the microbe and prevent its further action on the host. In indirect killing, neutrophils secrete cytokines that signal other innate and adaptive immune cells, which in turn become activated and start functioning towards the elimination of the prevailing infection.