A part of the immune system appears to help prion diseases spread to the brain, according to research in the April issue of Nature Medicine. Researchers hope that blocking this pathway may one day be a way to slow the disease.
Prions are misfolded forms of a normal protein and are responsible for brain-wasting diseases that include scrapie in sheep, "mad cow disease" in cows, and variant Creutzfeldt-Jakob disease in people. Animals and people can become infected when they ingest prions. Although it's clear that the immune system somehow helps the prions get to the brain, the exact mechanism isn't clear.
One possible culprit is the complement system, which marks invading pathogens by flagging them with certain proteins. The tags attract follicular dendritic cells (FDCs), which then trap the invaders and present them to the immune system. Previous work showed that prions accumulate on FDCs, so two teams of researchers wondered whether complements help prions get to the brain and cause disease.
In one of the studies, a team led by immunologist Mark Pepys of the Royal Free and University College Medical School in London, United Kingdom, treated mice with a protein from cobra venom that sops up a key complement protein. When scrapie prion protein was later injected into their abdomen, mice treated with venom came down with scrapie an average of 24 days later than control mice did.
In the other study, neuropathologist Adriano Aguzzi of the University of Zurich, Switzerland, and colleagues infected mice each missing the gene for one or more complement proteins or proteins that FDCs use to trap the complement complexes. When these animals were given low doses of scrapie, disease onset was delayed or in some cases even prevented, although large doses of prion could override the effect. The results suggest that blocking even just one part of the complement system could be a way to delay prion infections from reaching the brain.
The studies shed light on the early events in prion infection, according to virologist Suzette Priola of the National Institute of Allergy and Infectious Diseases' Rocky Mountain Laboratories in Hamilton, Montana. But she cautions that because the complement system is so important, blocking it could compromise a person's ability to fight other infections. "Unless you found something very specific, it may not be the best approach," Priola says.
--ALKA AGRAWAL
Related sites
General information about mad cow and variant Creutzfeldt-Jakob disease from the CDC
Mad cow disease information from the Ministry of Agriculture, Fisheries, and Food (U.K.)
