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Yale study explains complex infection fighting mechanism

Yale School of Medicine researchers report in Nature Immunology how infection fighting mechanisms in the body can distinguish between a virus and the healthy body, shedding new light on auto immune disorders.

The infection fighters in question, toll-like receptors (TLRs), function by recognizing viral, bacterial or fungal pathogens and then sending signals throughout the immune system announcing that an infection has occurred.

Viruses change features to avoid being recognized, thereby triggering the immune response. But TLRs recognize the highly conserved features of pathogens, features that are often difficult to change without affecting the punch of the pathogen, said lead author of the study, Gregory Barton of the University of California at Berkeley who performed the research while in the Section of Immunobiology at Yale School of Medicine.

He said that one exception to the general view of how TLRs work is the way TLRs recognize viruses since viruses lack the unique features of bacterial or fungal pathogens. Because of this, the immune system has had to find other ways to recognize viral infection.

"In particular, the DNA or RNA that comprise viral genomes can stimulate certain TLRs," Barton said. "This strategy comes at an enormous cost. By targeting the DNA or RNA of viruses, the immune system runs the risk of accidentally recognizing its own DNA and RNA as foreign and inappropriately making an immune response against itself. This autoimmune condition is called systemic lupus erythematosus or SLE, and can be devastating for those unfortunate enough to suffer from it."

The work of senior author Ruslan Medzhitov, professor of immunobiology, and his colleagues, has focused on trying to understand how recognition of a body's own DNA is avoided by those TLRs involved in viral nucleic acid recognition.

"We have known for some time that those TLRs are sequestered in specialized compartments within cells," Barton sa
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Contact: Jacqueline Weaver
jacqueline.weaver@yale.edu
203-432-8555
Yale University
10-Jan-2006


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