March 2004

Max-Planck-Gesellschaft

NETs protect against pathogenic bacteria



Stimulated neutrophil with NETs and some trapped Shigella (orange). Colored scanning electron micrograph.
Image: Max Planck Institute for Infection Biology




Specialized cells of our immune system, such as neutrophils, are the first line of defense against invading bacteria. They take up and destroy pathogenic microorganisms. New data from the Max Planck Institute for Infection Biology in Berlin show that neutrophils also have another, until now unknown defense mechanism: They can "spit out" a net-like structure that binds bacteria, disarms and finally kills them. These novel structures, called NETs (Neutrophil Extracellular Traps), were discovered by Professor Arturo Zychlinsky, director of the Department of Cellular Microbiology, and Volker Brinkmann's microscopy team. Their results will be published in the forthcoming edition of "Science" (Science, 5 March 2004).

Neutrophils make up the majority (50 - 80 per cent) of white blood cells. They possess granules, i. e. little vesicles which contain an arsenal of enzymatic and chemical weapons against microorganisms. When a neutrophil encounters a pathogen, it engulfs the microorganism. Once inside the neutrophil, the pathogen is killed by antimicrobial substances from the granules.

Berlin infection biologists have now discovered a totally new mechanism of defense: Surprisingly, neutrophils can also fight pathogens extracellularly by producing a net-like structure in which the microorganisms are trapped, disarmed and eventually killed. The scientists have called these structures NETs (for Neutrophil Extracellular Traps).



Bundle of NETs with trapped Shigella (orange). Colored scanning electron micrograph.
Image: Max Planck Institute for Infection Biology


NETs are very thin filaments that are visible in scanning electron microscopy (Fig. 1 and 2). The fibers are decorated with globular particles and bundle up to form more complex structures. One of the components of NETs is chromatin. This mixture of DNA and proteins is the repository of genetic information and normally resides in the cell nucleus. The main proteins in chromatin are histones: They are responsible for the ordered structure of DNA, and additionally, they are very efficient in killing bacteria. NETs also contain granule proteins from the neutrophils, which are crucial in disarming the bacteria.

In collaboration with Yvette Weinrauch from New York University, Arturo Zychlinsky and his colleagues could demonstrate that the NETs are very efficient in killing different bacteria: Shigella, the causative agent of dysentery, Salmonella, the etiological agent of typhoid fever, and Staphylococcus, a bacterium which causes diseases like food poisoning and toxic shock syndrome.

The scientists were able to find NETs in experimental cell cultures as well as in tissue samples of dysentery and human biopsies of appendicitis.

Original work:

Brinkmann V, Reichard U, Fauler B, Goosmann C, Uhlemann Y, Weiss D, Weinrauch Y, Zychlinsky A
Neutrophil extracellular traps kill bacteria
Science, 5 March 2004

A hi resolution link to Fig. 1 can be found here: http://www.mpg.de/bilderBerichteDokumente/multimedial/bilderWissenschaft/2004/02/Zychlinski1/presselogin/Web_Pressebild.jpeg
A hi resolution link to Fig. 2 can be found here: http://www.mpg.de/bilderBerichteDokumente/multimedial/bilderWissenschaft/2004/02/Zychlinski2/Web_Pressebild.jpeg


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