Neutrophil Extracellular Traps Kill Bacteria: Eports
Neutrophil Extracellular Traps Kill Bacteria: Eports
Neutrophil Extracellular Traps Kill Bacteria: Eports
Fig. 4. Analysis of tissue sections from experimental shigellosis in fibrous material staining for histones and DNA. (E) Staining for
rabbits (A to D) and spontaneous human appendicitis (E to H). (A) neutrophil elastase in an area of neutrophil exudate in human spon-
Immunofluorescence staining of histones reveals nuclear and extra- taneous appendicitis reveals fibrous extracellular material that also
cellular localization that largely overlaps with staining for DNA (C). stains for histone (F) and DNA (G). (H) Overlay of the images. The
(B) Staining with an antibody against Shigella-specific LPS. (D) The images are projections of confocal z stacks generated from sections of
overlay indicates that numerous Shigellae are closely associated to 5 to 6 m thickness. Bar, 50 m.
4.
and Clinical Correlates, J. I. Gallin, R Snyderman, Eds.
(Raven Press, New York, ed. 2, 1992), pp. 511–539.
L. C. Junqueira, J. Carneiro, R. O. Kelley, Basic Histol-
Emerging Vectors in the Culex
5.
6.
ogy (Appelton & Lange, Norwalk, CT, ed. 8, 1995).
D. F. Bainton, J. Immunol. Methods 232, 153 (1999).
N. Borregaard, J. B. Cowland, Blood 89, 3503 (1997).
pipiens Complex
7. C. Movitz, C. Dahlgren, Cell Biol. Int. 25, 963 (2001).
8. V. Brinkmann et al., data not shown.
Dina M. Fonseca,1,2* Nusha Keyghobadi,1 Colin A. Malcolm,3
9. M. J. Losman, T. M. Fasy, K. E. Novick, M. Monestier, Ceylan Mehmet,3 Francis Schaffner,4 Motoyoshi Mogi,5
J. Immunol. 148, 1561 (1992).
10. P. Salgame et al., Nucleic Acids Res. 25, 680 (1997).
Robert C. Fleischer,1 Richard C. Wilkerson2
11. P. L. Sabroe et al., J. Immunol. 170, 5268 (2003).
12. B. Fadeel et al., Blood 92, 4808 (1998). In the Old World, some mosquitoes in the Culex pipiens complex are excellent
13. N. A. Maianski, D. Roos, T. W. Kuijpers, Blood 101, enzootic vectors of West Nile virus, circulating the virus among birds, whereas
1987 (2002).
14. Y. Weinrauch et al., Nature 417, 91 (2002). others bite mainly humans and other mammals. Here we show that, in northern
15. J. G. Hirsch, J. Exp. Med. 108, 925 (1958). Europe, such forms differing in behavior and physiology have unique micro-
16. S. M. Zhdan-Pushkina, N. V. Dronova, Mikrobiologiia satellite fingerprints with no evidence of gene flow between them, as would be
45, 60 (1976).
17. H. S. Kim, C. B. Park, M. S. Kim, S. C. Kim, Biochem. expected from distinct species. In the United States, however, hybrids between
Biophys. Res. Commun. 229, 381 (1996). these forms are ubiquitous. Such hybrids between human-biters and bird-biters
18. P. Elsbach, J. Weiss, O. Levy, Trends Microbiol. 2, 324 may be the bridge vectors contributing to the unprecedented severity and range
(1994).
19. E. P. Reeves et al., Nature 416, 291 (2002). of the West Nile virus epidemic in North America.
20. V. Balloy et al., Am. J. Respir. Cell Mol. Biol. 28, 746 (2003).
21. The gift of M. Monestier, Temple University, the monoclo- Species in the Culex pipiens complex are overwintering mosquitoes can serve as a
nal antibody against H2A-H2B-DNA, is gratefully acknowl- considered to be the primary vectors of source of WNV to initiate an infection
edged. The authors thank the help of M. Ingersoll, B.
Raupach, C. Scharff, C. Heinz, and members of the Depart- West Nile virus (WNV) in North America cycle in the spring (7 ). Blood-meal analysis
ment of Cellular Microbiology, Max Planck Institute for because they are often the most common has revealed that Cx. pipiens in the United
Infection Biology. Supported in part by NIH grant mosquitoes in urban areas (1), because dis- States bite both humans (anthropophagy)
AI037720.
ease outbreaks occur during their peak and birds, suggesting they may serve as
Supporting Online Material abundance period (2), because they are bridge vectors of the disease from birds to
www.sciencemag.org/cgi/content/full/303/5663/1532/DC1
Materials and Methods competent laboratory vectors of WNV (3), humans (2). Human WNV epidemics re-
Figs. S1 to S3 and because field populations in the United quire bridge vectors, because humans and
Table S1 States have repeatedly been found infected other mammals do not usually generate
Movies S1 and S2
with the virus (4, 5). In addition, they can high enough viremia to infect biting mos-
9 October 2003; accepted 24 December 2003 transmit the virus transovarially (6 ), so quitoes (8). Although Cx. pipiens has been