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 journalArticle

209 Citations (Scopus)

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

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Hydroxymethylglutaryl-CoA Reductase Inhibitors
Phagocytes
Bacterial Infections
Respiratory Burst
Sterols
Phagocytosis
Staphylococcus aureus
Extracellular Traps
Epidemiologic Studies
Monocytes
Oxidoreductases
Neutrophils
Macrophages
Cholesterol
Drug Therapy
Mortality
Enzymes

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Virology

Cite this

Chow, O. A., Von Köckritz-Blickwede, M., Bright, A. T., Hensler, M. E., Zinkernagel, A. S., Cogen, A. L., ... Nizet, V. (2010). Statins enhance formation of phagocyte extracellular traps. Cell Host and Microbe, 8(5), 445-454. https://doi.org/10.1016/j.chom.2010.10.005
Chow, Ohn A. ; Von Köckritz-Blickwede, Maren ; Bright, A. Taylor ; Hensler, Mary E. ; Zinkernagel, Annelies S. ; Cogen, Anna L. ; Gallo, Richard L. ; Monestier, Marc ; Wang, Yanming ; Glass, Christopher K. ; Nizet, Victor. / Statins enhance formation of phagocyte extracellular traps. In: Cell Host and Microbe. 2010 ; Vol. 8, No. 5. pp. 445-454.
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Chow, OA, Von Köckritz-Blickwede, M, Bright, AT, Hensler, ME, Zinkernagel, AS, Cogen, AL, Gallo, RL, Monestier, M, Wang, Y, Glass, CK & Nizet, V 2010, 'Statins enhance formation of phagocyte extracellular traps', Cell Host and Microbe, vol. 8, no. 5, pp. 445-454. https://doi.org/10.1016/j.chom.2010.10.005

Statins enhance formation of phagocyte extracellular traps. / Chow, Ohn A.; Von Köckritz-Blickwede, Maren; Bright, A. Taylor; Hensler, Mary E.; Zinkernagel, Annelies S.; Cogen, Anna L.; Gallo, Richard L.; Monestier, Marc; Wang, Yanming; Glass, Christopher K.; Nizet, Victor.

In: Cell Host and Microbe, Vol. 8, No. 5, 18.11.2010, p. 445-454.

Research output: Contribution to journalArticle

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AU - Chow, Ohn A.

AU - Von Köckritz-Blickwede, Maren

AU - Bright, A. Taylor

AU - Hensler, Mary E.

AU - Zinkernagel, Annelies S.

AU - Cogen, Anna L.

AU - Gallo, Richard L.

AU - Monestier, Marc

AU - Wang, Yanming

AU - Glass, Christopher K.

AU - Nizet, Victor

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Chow OA, Von Köckritz-Blickwede M, Bright AT, Hensler ME, Zinkernagel AS, Cogen AL et al. Statins enhance formation of phagocyte extracellular traps. Cell Host and Microbe. 2010 Nov 18;8(5):445-454. https://doi.org/10.1016/j.chom.2010.10.005