Effector Mechanisms of Neutrophils within the Innate Immune System in Response to Mycobacterium tuberculosis Infection.
Neutrophils have a significant yet controversial role in the innate immune response toMycobacterium tuberculosis(M. tb) infection, which is not yet fully understood. In addition to neutrophils' well-known effector mechanisms, they may also help control infection ofM. tbthrough the formation of neutrophil extracellular traps (NETs), which are thought to further promote the killing ofM. tbby 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 withM. tband other bacterial and chronic rheumatological diseases such as Systemic Lupus Erythematosus. Adversely, during the innate immune response toM. 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 killM. 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 offM. tbinfection. 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 containM. tbinfection 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 calledM. smegmatis-Ag85C-MPT51-HspX (mc²-CMX) that has been shown to elicit a humoral and cellular response againstM. tbin mice that is superior to the BCG vaccine.
Department of Basic Medical Sciences, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, 309 East Second Street, Pomona, CA 91766-1854, USA. ewarren@westernu.edu.
Eric
E
Warren
Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA 91766-1854, USA. gteskey@westernu.edu.
Garrett
G
Teskey
Department of Basic Medical Sciences, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, 309 East Second Street, Pomona, CA 91766-1854, USA. vvenketaraman@westernu.edu.|Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA 91766-1854, USA. vvenketaraman@westernu.edu.
Vishwanath
V
Venketaraman
Cytokines; Innate immunity; M. tb; Mycobacterium tuberculosis; NETs; Neutrophils; PMN; Phagocytosis-induced cell death; TB; Tuberculosis; polymorphonuclear leukocytes