Innate Immune Cells and Hypertension: Neutrophils and Neutrophil Extracellular Traps (NETs)

Compr Physiol. 2021 Feb 12;11(1):1575-1589. doi: 10.1002/cphy.c200020.


Uncontrolled immune system activation amplifies end-organ injury in hypertension. Nonetheless, the exact mechanisms initiating this exacerbated inflammatory response, thereby contributing to further increases in blood pressure (BP), are still being revealed. While participation of lymphoid-derived immune cells has been well described in the hypertension literature, the mechanisms by which myeloid-derived innate immune cells contribute to T cell activation, and subsequent BP elevation, remains an active area of investigation. In this article, we critically analyze the literature to understand how monocytes, macrophages, dendritic cells, and polymorphonuclear leukocytes, including mast cells, eosinophils, basophils, and neutrophils, contribute to hypertension and hypertension-associated end-organ injury. The most abundant leukocytes, neutrophils, are indisputably increased in hypertension. However, it is unknown how (and why) they switch from critical first responders of the innate immune system, and homeostatic regulators of BP, to tissue-damaging, pro-hypertensive mediators. We propose that myeloperoxidase-derived pro-oxidants, neutrophil elastase, neutrophil extracellular traps (NETs), and interactions with other innate and adaptive immune cells are novel mechanisms that could contribute to the inflammatory cascade in hypertension. We further posit that the gut microbiota serves as a set point for neutropoiesis and their function. Finally, given that hypertension appears to be a key risk factor for morbidity and mortality in COVID-19 patients, we put forth evidence that neutrophils and NETs cause cardiovascular injury post-coronavirus infection, and thus may be proposed as an intriguing therapeutic target for high-risk individuals. © 2021 American Physiological Society. Compr Physiol 11:1575-1589, 2021.

Keywords: COVID-19; blood pressure; gut microbiota; immune system; myeloid-derived immune cells; neutrophils; oxidative stress.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • COVID-19* / complications
  • COVID-19* / immunology
  • Extracellular Traps / immunology*
  • Gastrointestinal Microbiome / immunology
  • Humans
  • Hypertension / immunology*
  • Hypertension / physiopathology
  • Immunity, Innate / immunology*
  • Inflammation / immunology
  • Inflammation / physiopathology
  • Neutrophils / immunology*
  • Oxidative Stress / immunology
  • SARS-CoV-2 / immunology