title: Neutrophil extracellular traps entrap and kill Borrelia burgdorferi sensu stricto spirochetes and are not affected by Ixodes ricinus tick saliva.
abstract: Lyme disease is caused by spirochetes of the Borrelia burgdorferi sensu lato complex. They are transmitted mainly by Ixodes ricinus ticks. After a few hours of infestation, neutrophils massively infiltrate the bite site. They can kill Borrelia via phagocytosis, oxidative burst, and hydrolytic enzymes. However, factors in tick saliva promote propagation of the bacteria in the host even in the presence of a large number of neutrophils. The neutrophil extracellular trap (NET) consists in the extrusion of the neutrophil's own DNA, forming traps that can retain and kill bacteria. The production of reactive oxygen species is apparently associated with the onset of NETs (NETosis). In this article, we describe NET formation at the tick bite site in vivo in mice. We show that Borrelia burgdorferi sensu stricto spirochetes become trapped and killed by NETs in humans and that the bacteria do not seem to release significant nucleases to evade this process. Saliva from I. ricinus did not affect NET formation by human neutrophils or its stability. However, it greatly decreased neutrophil reactive oxygen species production, suggesting that a strong decrease of hydrogen peroxide does not affect NET formation. Finally, round bodies trapped in NETs were observed, some of them staining as live bacteria. This observation could help contribute to a better understanding of the early steps of Borrelia invasion and erythema migrans formation after tick bite.
authors.affiliation: Laboratory of Human Histology-Centre de Recherche sur les Protéines Prion, University of Liège, B-4000 Liège, Belgium.
authors.forename: Catherine
authors.initials: C
authors.lastname: Menten-Dedoyart
authors.forename: Céline
authors.initials: C
authors.lastname: Faccinetto
authors.forename: Maryna
authors.initials: M
authors.lastname: Golovchenko
authors.forename: Ingrid
authors.initials: I
authors.lastname: Dupiereux
authors.forename: Pierre-Bernard
authors.initials: PB
authors.lastname: Van Lerberghe
authors.forename: Sophie
authors.initials: S
authors.lastname: Dubois
authors.forename: Christophe
authors.initials: C
authors.lastname: Desmet
authors.forename: Benaissa
authors.initials: B
authors.lastname: Elmoualij
authors.forename: Frédéric
authors.initials: F
authors.lastname: Baron
authors.forename: Nataliia
authors.initials: N
authors.lastname: Rudenko
authors.forename: Cécile
authors.initials: C
authors.lastname: Oury
authors.forename: Ernst
authors.initials: E
authors.lastname: Heinen
authors.forename: Bernard
authors.initials: B
authors.lastname: Couvreur
mesh_terms: D000818:Animals; D001096:Arachnid Vectors / Q000276:immunology* / Q000382:microbiology; D001733:Bites and Stings; D015748:Borrelia burgdorferi Group / Q000502:physiology*; D004247:DNA / Q000276:immunology; D005260:Female; D005929:Glossitis, Benign Migratory / Q000150:complications / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D006801:Humans; D018884:Ixodes / Q000276:immunology* / Q000382:microbiology; D008193:Lyme Disease / Q000150:complications / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D008297:Male; D051379:Mice; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000276:immunology; D012463:Saliva / Q000737:chemistry / Q000276:immunology*
chemical_list: D017382:Reactive Oxygen Species; D004247:DNA