Neutrophil Extracellular Traps (NET) Entrap and Kill Borrelia burgdorferi sensu stricto Spirochetes and Are not Affected by Ixodes ricinus Tick Saliva.
[en] Lyme disease is a pathology caused by members of the Borrelia burgdorferi sensu lato (s.l.) complex, most often by B. burgdorferi sensu stricto (s.s.). 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. 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 (ROS) is apparently associated with the onset of NEtosis. Here we describe NETs formation at the tick bite site in vivo in mice. We show that Borrelia burgdorferi s.s. 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 neutrophiles or it stability. However, it strongly decreased neutrophil ROS production, suggesting that a strong decrease of hydrogen peroxide does not affect NET formation. Finally, round bodies were observed trapped in NETs, some of them staining as live cells. This observation could help contribute to a better explanation of erythema migrans.
Menten, Catherine ; Centre Hospitalier Universitaire de Liège - CHU > Centre d'oncologie
Faccinetto, Céline ; Université de Liège - ULiège > Sciences Biomédicales et Précliniques > Génétique Humaine
Golovchenko, Maryna; Institute of Parasitology, Branisovska > Biology Center
Dupiereux-Fettweis, Ingrid ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Histologie
Van Lerberghe, Pierre-Bernard ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques
DUBOIS, Sophie ; Centre Hospitalier Universitaire de Liège - CHU > Centre d'oncologie
Desmet, Christophe ; Université de Liège - ULiège > Département de sciences fonctionnelles > Physiologie
Elmoualij, Benaïssa ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Histologie
Rudenko, Nataliia; Institute of Parasitology, Branisovska > Biology Center
Oury, Cécile ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > GIGA-R : Génétique humaine
Heinen, Ernst ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques
Neutrophil Extracellular Traps (NET) Entrap and Kill Borrelia burgdorferi sensu stricto Spirochetes and Are not Affected by Ixodes ricinus Tick Saliva.
Publication date :
December 2012
Journal title :
Journal of Immunology
ISSN :
0022-1767
eISSN :
1550-6606
Publisher :
American Association of Immunologists, Baltimore, United States - Maryland
Rudenko, N., M. Golovchenko, L. Grubhoffer, and J. H. Oliver, Jr. 2011. Updates on Borrelia burgdorferi sensu lato complex with respect to public health. Ticks Tick Borne Dis. 2: 123-128.
Murray, T. S., and E. D. Shapiro. 2010. Lyme disease. Clin. Lab. Med. 30: 311-328.
Schuijt, T. J., J. W. Hovius, T. van der Poll, A. P. van Dam, and E. Fikrig. 2011. Lyme borreliosis vaccination: the facts, the challenge, the future. Trends Parasitol. 27: 40-47.
Wikel, S. K. 1996. Host immunity to ticks. Annu. Rev. Entomol. 41: 1-22.
Amosova, L. I. 1994. [The ultrastructural characteristics of the histopathological changes at the site of attachment to the host body of larvae of the ixodid tick Ixodes ricinus]. Parazitologia 28: 356-363.
Brinkmann, V., U. Reichard, C. Goosmann, B. Fauler, Y. Uhlemann, D. S. Weiss, Y. Weinrauch, and A. Zychlinsky. 2004. Neutrophil extracellular traps kill bacteria. Science 303: 1532-1535. (Pubitemid 38314426)
Fuchs, T. A., U. Abed, C. Goosmann, R. Hurwitz, I. Schulze, V. Wahn, Y.Weinrauch, V. Brinkmann, and A. Zychlinsky. 2007. Novel cell death program leads to neutrophil extracellular traps. J. Cell Biol. 176: 231-241. (Pubitemid 46143263)
Metzler, K. D., T. A. Fuchs, W. M. Nauseef, D. Reumaux, J. Roesler, I. Schulze, V. Wahn, V. Papayannopoulos, and A. Zychlinsky. 2011. Myeloperoxidase is required for neutrophil extracellular trap formation: implications for innate immunity. Blood 117: 953-959.
Lusitani, D., S. E. Malawista, and R. R. Montgomery. 2002. Borrelia burgdorferi are susceptible to killing by a variety of human polymorphonuclear leukocyte components. J. Infect. Dis. 185: 797-804. (Pubitemid 34226207)
Hartiala, P., J. Hytönen, J. Suhonen, O. Leppäranta, H. Tuominen-Gustafsson, and M. K. Viljanen. 2008. Borrelia burgdorferi inhibits human neutrophil functions. Microbes Infect. 10: 60-68.
Malawista, S. E., and C. A. De Boisfleury. 2008. Clocking the Lyme spirochete. PLoS. One 3: e1633.
Brorson, O., S. H. Brorson, J. Scythes, J. MacAllister, A. Wier, and L. Margulis. 2009. Destruction of spirochete Borrelia burgdorferi round-body propagules (RBs) by the antibiotic tigecycline. Proc. Natl. Acad. Sci. USA 106: 18656-18661.
Stricker, R. B., and L. Johnson. 2011. Lyme disease: the next decade. Infect. Drug Resist. 4: 1-9.
Horká, H., K. Cerná-Kýcková, A. Skallová, and J. Kopecký. 2009. Tick saliva affects both proliferation and distribution of Borrelia burgdorferi spirochetes in mouse organs and increases transmission of spirochetes to ticks. Int. J. Med. Microbiol. 299: 373-380.
Menten-Dedoyart, C., B. Couvreur, O. Thellin, P. V. Drion, M. Herry, O. Jolois, and E. Heinen. 2008. Influence of the Ixodes ricinus tick blood-feeding on the antigen-specific antibody response in vivo. Vaccine 26: 6956-6964.
Beaufays, J., B. Adam, C. Menten-Dedoyart, L. Fievez, A. Grosjean, Y. Decrem, P. P. Prévôt, S. Santini, R. Brasseur, M. Brossard, et al. 2008. Ir-LBP, an Ixodes ricinus tick salivary LTB4-binding lipocalin, interferes with host neutrophil function. PLoS. One 3: e3987.
Xu, Q., S. V. Seemanapalli, K. E. Reif, C. R. Brown, and F. T. Liang. 2007. Increasing the recruitment of neutrophils to the site of infection dramatically attenuates Borrelia burgdorferi infectivity. J. Immunol. 178: 5109-5115. (Pubitemid 46595294)
Ribeiro, J. M., J. J. Weis, and S. R. Telford, III. 1990. Saliva of the tick Ixodes dammini inhibits neutrophil function. Exp. Parasitol. 70: 382-388. (Pubitemid 20230663)
Guo, X., C. J. Booth, M. A. Paley, X. Wang, K. DePonte, E. Fikrig, S. Narasimhan, and R. R. Montgomery. 2009. Inhibition of neutrophil function by two tick salivary proteins. Infect. Immun. 77: 2320-2329.
Leboulle, G., M. Crippa, Y. Decrem, N. Mejri, M. Brossard, A. Bollen, and E. Godfroid. 2002. Characterization of a novel salivary immunosuppressive protein from Ixodes ricinus ticks. J. Biol. Chem. 277: 10083-10089. (Pubitemid 34968118)
Cluss, R. G., D. A. Silverman, and T. R. Stafford. 2004. Extracellular secretion of the Borrelia burgdorferi Oms28 porin and Bgp, a glycosaminoglycan binding protein. Infect. Immun. 72: 6279-6286. (Pubitemid 39425405)
Berends, E. T., A. R. Horswill, N. M. Haste, M. Monestier, V. Nizet, and M. von Köckritz-Blickwede. 2010. Nuclease expression by Staphylococcus aureus facilitates escape from neutrophil extracellular traps. J. Innate Immun. 2: 576-586.
Mejri, N., B. Rutti, and M. Brossard. 2002. Immunosuppressive effects of Ixodes ricinus tick saliva or salivary gland extracts on innate and acquired immune response of BALB/c mice. Parasitol. Res. 88: 192-197. (Pubitemid 34146595)
Cornell, K. A., S. Primus, J. A. Martinez, and N. Parveen. 2009. Assessment of methylthioadenosine/S-adenosylhomocysteine nucleosidases of Borrelia burgdorferi as targets for novel antimicrobials using a novel high-throughput method. J. Antimicrob. Chemother. 63: 1163-1172.
Kuthejlová, M., J. Kopecký, G. Stepánová, and A. Macela. 2001. Tick salivary gland extract inhibits killing of Borrelia afzelii spirochetes by mouse macrophages. Infect. Immun. 69: 575-578. (Pubitemid 32038362)
Nishinaka, Y., T. Arai, S. Adachi, A. Takaori-Kondo, and K. Yamashita. 2011. Singlet oxygen is essential for neutrophil extracellular trap formation. Biochem. Biophys. Res. Commun. 413: 75-79.
Fivaz, B. H. 1989. Immune suppression induced by the brown ear tick Rhipicephalus appendiculatus Neumann, 1901. J. Parasitol. 75: 946-952. (Pubitemid 20099170)
Beiter, K., F. Wartha, B. Albiger, S. Normark, A. Zychlinsky, and B. Henriques- Normark. 2006. An endonuclease allows Streptococcus pneumoniae to escape from neutrophil extracellular traps. Curr. Biol. 16: 401-407. (Pubitemid 43259351)
Buchanan, J. T., A. J. Simpson, R. K. Aziz, G. Y. Liu, S. A. Kristian, M. Kotb, J. Feramisco, and V. Nizet. 2006. DNase expression allows the pathogen group A Streptococcus to escape killing in neutrophil extracellular traps. Curr. Biol. 16: 396-400. (Pubitemid 43259350)
Sumby, P., K. D. Barbian, D. J. Gardner, A. R. Whitney, D. M. Welty, R. D. Long, J. R. Bailey, M. J. Parnell, N. P. Hoe, G. G. Adams, et al. 2005. Extracellular deoxyribonuclease made by group A Streptococcus assists pathogenesis by enhancing evasion of the innate immune response. Proc. Natl. Acad. Sci. USA 102: 1679-1684. (Pubitemid 40209227)
Mulcahy, H., L. Charron-Mazenod, and S. Lewenza. 2010. Pseudomonas aeruginosa produces an extracellular deoxyribonuclease that is required for utilization of DNA as a nutrient source. Environ. Microbiol. 12: 1621-1629.
Uchiyama, S., F. Andreoni, R. A. Schuepbach, V. Nizet, and A. S. Zinkernagel. 2012. DNase Sda1 allows invasive M1T1 Group A Streptococcus to prevent TLR9-dependent recognition. PLoS. Pathog. 8: e1002736.
von Köckritz-Blickwede, M., O. A. Chow, and V. Nizet. 2009. Fetal calf serum contains heat-stable nucleases that degrade neutrophil extracellular traps. Blood 114: 5245-5246.
Alban, P. S., P. W. Johnson, and D. R. Nelson. 2000. Serum-starvation- induced changes in protein synthesis and morphology of Borrelia burgdorferi. Microbiology 146: 119-127. (Pubitemid 30066313)
Dunham-Ems, S. M., M. J. Caimano, C. H. Eggers, and J. D. Radolf. 2012. Borrelia burgdorferi requires the alternative sigma factor RpoS for dissemination within the vector during tick-to-mammal transmission. PLoS. Pathog. 8:e1002532.