Abstract
Neutrophils have a significant yet controversial role in the innate immune response to Mycobacterium tuberculosis (M. tb) infection, which is not yet fully understood. In addition to neutrophils’ well-known effector mechanisms, they may also help control infection of M. tb through the formation of neutrophil extracellular traps (NETs), which are thought to further promote the killing of M. tb by resident alveolar macrophages. Cytokines such as IFN-γ have now been shown to serve an immunomodulatory role in neutrophil functioning in conjunction to its pro-inflammatory function. Additionally, the unique transcriptional changes of neutrophils may be used to differentiate between infection with M. tb and other bacterial and chronic rheumatological diseases such as Systemic Lupus Erythematosus. Adversely, during the innate immune response to M. tb, inappropriate phagocytosis of spent neutrophils can result in nonspecific damage to host cells due to necrotic lysis. Furthermore, some individuals have been shown to be more genetically susceptible to tuberculosis (TB) due to a “Trojan Horse” phenomenon whereby neutrophils block the ability of resident macrophages to kill M. tb. Despite these aforementioned negative consequences, through the scope of this review we will provide evidence to support the idea that neutrophils, while sometimes damaging, can also be an important component in warding off M. tb infection. This is exemplified in immunocompromised individuals, such as those with human immunodeficiency virus (HIV) infection or Type 2 diabetes mellitus. These individuals are at an increased risk of developing tuberculosis (TB) due to a diminished innate immune response associated with decreased levels of glutathione. Consequently, there has been a worldwide effort to limit and contain M. tb infection through the use of antibiotics and vaccinations. However, due to several significant limitations, the current bacille Calmette-Guerin vaccine (BCG, vaccine against TB) does not meet the criteria for universal utilization for all ages and populations across the globe. New research involving neutrophils has yielded a new vaccine called M. smegmatis-Ag85C-MPT51-HspX (mc2-CMX) that has been shown to elicit a humoral and cellular response against M. tb in mice that is superior to the BCG vaccine.
Highlights
Tuberculosis (TB) is an infectious disease that caused 10.4 million illnesses and 1.8 million deaths worldwide in 2015 [1]
The focus of early immunologists was aimed at understanding mononuclear phagocytes such as monocytes and macrophages, despite the fact that neutrophils constitute approximately 50% to 80% of all circulating white blood cells and contribute to the innate immune response via phagocytosis of invading bacteria, degranulation, and subsequent secretion of cytokines such as tumor-necrosis factor-alpha (TNF-α) and interleukin 1 (IL-1) [7,10,11,12,13,14,15,16]
The difference in susceptibility to M. tb between these two genetic variants largely consisted of differing neutrophilic functioning within the lungs of mice that were challenged with M. tb
Summary
Tuberculosis (TB) is an infectious disease that caused 10.4 million illnesses and 1.8 million deaths worldwide in 2015 [1]. In addition to the various treatment regimens for TB, the immune system plays an integral role in defense against M. tb infection [4,5]. Innate immune cells such as polymorphonuclear leukocytes (PMN), or neutrophils have been shown to be circumstantially unfavorable during M. tb infection [6]. They have been shown to help mediate an early inflammatory response that is critical for controlling M. tb infection [7,8,9]. Neutrophils secrete reactive oxygen species (ROS), elastase, collagenase, and myeloperoxidase, factors that have been shown to damage both invading mycobacterial cells and host cells in a nonselective manner [9,16,17]
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