Editors' ChoiceImmunology

Neutrophil NETs drive atherosclerosis

Sci. Signal.  21 Jul 2015:
Vol. 8, Issue 386, pp. ec199
DOI: 10.1126/scisignal.aad0389

The buildup of fats, cholesterol, and other substances in arteries causes atherosclerosis, which restricts blood flow and can lead to heart attacks and stroke. Inflammation contributes to the pathogenesis of atherosclerosis, but exactly how is not fully understood. Warnatsch et al. now show that immune cells called neutrophils release NETs (neutrophil extracellular traps) (see the Perspective by Nahrendorf and Swirski). These NETs are composed of DNA and antimicrobial proteins, and in the setting of atherosclerosis they activate innate immune signaling pathways in macrophages. This causes the macrophages to secrete proinflammatory cytokines, exacerbating the disease. Indirectly, NETS also attract a specialized subset of T cells that further amplify the proinflammatory response.

A. Warnatsch, M. Ioannou, Q. Wang, V. Papayannopoulos, Neutrophil extracellular traps license macrophages for cytokine production in atherosclerosis. Science 349, 316–320 (2015). [Abstract] [Full Text]

M. Nahrendorf, F. K. Swirski, Neutrophil-macrophage communication in inflammation and atherosclerosis. Science 349, 237–238 (2015). [Abstract] [Full Text]