title: Statins enhance formation of phagocyte extracellular traps.
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.
authors.affiliation: Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Ohn A
authors.initials: OA
authors.lastname: Chow
authors.forename: Maren
authors.initials: M
authors.lastname: von Köckritz-Blickwede
authors.forename: A Taylor
authors.initials: AT
authors.lastname: Bright
authors.forename: Mary E
authors.initials: ME
authors.lastname: Hensler
authors.forename: Annelies S
authors.initials: AS
authors.lastname: Zinkernagel
authors.forename: Anna L
authors.initials: AL
authors.lastname: Cogen
authors.forename: Richard L
authors.initials: RL
authors.lastname: Gallo
authors.forename: Marc
authors.initials: M
authors.lastname: Monestier
authors.forename: Yanming
authors.initials: Y
authors.lastname: Wang
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Glass
authors.forename: Victor
authors.initials: V
authors.lastname: Nizet
mesh_terms: D000214:Acyl Coenzyme A / Q000037:antagonists & inhibitors; D000818:Animals; D002478:Cells, Cultured; D004269:DNA, Bacterial / Q000187:drug effects / Q000276:immunology; D005110:Extracellular Space / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000382:microbiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018181:Mice, Inbred CFTR; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology / Q000382:microbiology; D010586:Phagocytes / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D011023:Pneumonia, Staphylococcal / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects*
chemical_list: D000214:Acyl Coenzyme A; D004269:DNA, Bacterial; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C008047:3-hydroxy-3-methylglutaryl-coenzyme A