title: Neutrophil Extracellular Traps are Involved in the Innate Immune Response to Infection with Leptospira.
abstract: NETosis is a process by which neutrophils extrude their DNA together with bactericidal proteins that trap and/or kill pathogens. In the present study, we evaluated the ability of Leptospira spp. to induce NETosis using human ex vivo and murine in vivo models. Microscopy and fluorometric studies showed that incubation of human neutrophils with Leptospira interrogans serovar Copenhageni strain Fiocruz L1-130 (LIC) resulted in the release of DNA extracellular traps (NETs). The bacteria number, pathogenicity and viability were relevant factors for induction of NETs, but bacteria motility was not. Entrapment of LIC in the NETs resulted in LIC death; however, pathogenic but not saprophytic Leptospira sp. exerted nuclease activity and degraded DNA. Mice infected with LIC showed circulating NETs after 2 days post-infection (dpi). Depletion of neutrophils with mAb1A8 significantly reduced the amount of intravascular NETs in LIC-infected mice, increasing bacteremia at 3 dpi. Although there was a low bacterial burden, scarce neutrophils and an absence of inflammation in the early stages of infection in the kidney and liver, at the beginning of the leptospiruric phase, the bacterial burden was significantly higher in kidneys of neutrophil-depleted-mice compared to non-depleted and infected mice. Surprisingly, interstitial nephritis was of similar intensity in both groups of infected mice. Taken together, these data suggest that LIC triggers NETs, and that the intravascular formation of these DNA traps appears to be critical not only to prevent early leptospiral dissemination but also to preclude further bacterial burden.
authors.affiliation: Laboratory of Animal Viruses, Institute of Biotechnology and Molecular Biology, CCT-La Plata, CONICET-UNLP, Buenos Aires, Argentina.
authors.forename: Emilia
authors.initials: E
authors.lastname: Scharrig
authors.affiliation: Laboratory of Experimental Thrombosis, Institute of Experimental Medicine, CONICET-National Academy of Medicine, Buenos Aires, Argentina.
authors.forename: Agostina
authors.initials: A
authors.lastname: Carestia
authors.affiliation: Laboratory of Animal Viruses, Institute of Biotechnology and Molecular Biology, CCT-La Plata, CONICET-UNLP, Buenos Aires, Argentina.
authors.forename: María F
authors.initials: MF
authors.lastname: Ferrer
authors.affiliation: Laboratory of Animal Viruses, Institute of Biotechnology and Molecular Biology, CCT-La Plata, CONICET-UNLP, Buenos Aires, Argentina.
authors.forename: Maia
authors.initials: M
authors.lastname: Cédola
authors.affiliation: Laboratory of Animal Viruses, Institute of Biotechnology and Molecular Biology, CCT-La Plata, CONICET-UNLP, Buenos Aires, Argentina.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Pretre
authors.affiliation: Division of Pathology, Children Hospital "Superiora Sor María Ludovica", La Plata, Argentina; Cátedra de Patología "A", Facultad de Medicina, Universidad Nacional de La Plata, La Plata, Argentina.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Drut
authors.affiliation: Institut Pasteur, Biology of Spirochetes Unit, Paris, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Picardeau
authors.affiliation: Laboratory of Experimental Thrombosis, Institute of Experimental Medicine, CONICET-National Academy of Medicine, Buenos Aires, Argentina.
authors.forename: Mirta
authors.initials: M
authors.lastname: Schattner
authors.affiliation: Laboratory of Animal Viruses, Institute of Biotechnology and Molecular Biology, CCT-La Plata, CONICET-UNLP, Buenos Aires, Argentina.
authors.forename: Ricardo M
authors.initials: RM
authors.lastname: Gómez
mesh_terms: D000818:Animals; D065206:Extracellular Traps / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D007919:Leptospira / Q000276:immunology / Q000502:physiology*; D007922:Leptospirosis / Q000276:immunology* / Q000382:microbiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology* / Q000382:microbiology