Statins enhance formation of phagocyte extracellular traps

Ohn A. Chow, Maren Von Köckritz-Blickwede, A. Taylor Bright, Mary E. Hensler, Annelies S. Zinkernagel, Anna L. Cogen, Richard L. Gallo, Marc Monestier, Yanming Wang, Christopher K. Glass, Victor Nizet

Research output: Contribution to journalArticlepeer-review

243 Scopus citations

Abstract

Statins are inhibitors of 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in cholesterol biosynthesis. Recent clinico-epidemiologic studies correlate patients receiving statin therapy with having reduced mortality associated with severe bacterial infection. Investigating the effect of statins on the innate immune capacity of phagocytic cells against the human pathogen Staphylococcus aureus, we uncovered a beneficial effect of statins on bacterial clearance by phagocytes, although, paradoxically, both phagocytosis and oxidative burst were inhibited. Probing instead for an extracellular mechanism of killing, we found that statins boosted the production of antibacterial DNA-based extracellular traps (ETs) by human and murine neutrophils and also monocytes/macrophages. The effect of statins to induce phagocyte ETs was linked to sterol pathway inhibition. We conclude that a drug therapy taken chronically by millions alters the functional behavior of phagocytic cells, which could have ramifications for susceptibility and response to bacterial infections in these patients.

Original languageEnglish (US)
Pages (from-to)445-454
Number of pages10
JournalCell Host and Microbe
Volume8
Issue number5
DOIs
StatePublished - Nov 18 2010

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Virology

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