Viruses take many dirty tricks to evade our immune defenses and make us sick, but now scientists have developed a trick of their own. The researchers found that cells incentive to fight against bacteria may also help fight against the virus, even if the cells would probably not the right weapons to do so. "It would be like in a football match, the arming of the defense with baseball bats," said Andrew Gewirtz, an immunologist at the lining of Georgia State University in Atlanta. The discovery may solve a mystery of vaccines and lead to new ways to fight against infectious diseases.
Your cells do not respond in the same way for bacteria and viruses. They spend on different genes and different mixtures release of chemical messengers and protective molecules. Therefore Gewirtz and his colleagues were surprised by the results of an experiment they carried out 6 years ago. Researchers were testing if a flagellin injection, a protein that is part of the tail (or flagella) some bacteria use to propel the active antibacterial defenses of the body. Their results showed that he did, allowing mice to survive then what would have been a lethal dose of harmful intestinal bacteria.
The surprise came when the team Gewirtz infected mice with rotavirus, a common cause of severe diarrhea in young children. Although the virus has no flagellum, rodents injected with flagellin in advance protection against the pathogen.
In their new study, published online today in Science , Gewirtz and his colleagues understood why. Researchers determined that both detection of pathogenic molecules allow cells to recognize flagellin injected. When cells detect flagellin, they stimulate other cells to emit interleukin-22 (IL-22) and interleukin-18 (IL-18), the molecular signals that help orchestrate a defensive response. It would probably help kill bacterial invaders, but why does it work against viruses?
The answer may lie in the habits of rotavirus, which invades the cells lining the small intestine. IL-22 makes the intestinal cells more resistant to viral invasion, whereas IL-18 defeats the virus by stimulating the cells it has already infected suicide. Thus, when these molecules are activated, they fight bacteria and rotavirus. Indeed, injecting mice with IL-22 and IL-18 triggered the same antiviral effect that flagellin, the team found.
Gewirtz says this mechanism might work because "it is not that the virus is used to." Rotavirus has evolved to circumvent the antiviral defenses of the body, but it can not compensate for the response activated by flagellin or combination of iL-22 and iL-18.
"It is a very well documented history," said Roger Glass, rotavirologist the National Institutes of Health in Bethesda, Maryland. " they work through all the possible explanations. " The crossing protection the authors observed is unexpected because the opposite often happens, says immunologist and physician Robert Sabat of Medicine Charité University in Berlin. For example, viral chest infections often leave patients vulnerable to bacterial infections, not less.
Glass adds that the results may solve a mystery on the two new oral rotavirus vaccines introduced in the last decade. Vaccines contain weakened forms of the virus and are more effective in developed countries than in developing countries, where rotavirus kills more than 400,000 children each year. developing country children were probably exposed to more carriers flagella bacteria when they are vaccinated, he said. As a result, their cells could destroy the rotavirus vaccine in the front can develop immunity.
Researchers do not expect the discovery to have much impact on overall mortality against rotavirus infections. Treating children with IL-22 and IL-18 would not be possible in developing countries where the virus is a major cause of death because of their limited medical facilities, said Glass. In developed countries, although the combination may benefit children and adults whose immune system is weakened because of the treatment or diseases like AIDS and cancer that are vulnerable to rotavirus infection.
Sabat notes that researchers have already conducted clinical trials of IL-22 and IL-18 in patients with cancer, and IL-18 did cause side effects such as fever, nausea and difficulty breathing. However, he said, "a combination of IL-22 and low-dose IL-18 could be well tolerated."
IL-22 and IL-18 could have other uses as well. "We think the system we have developed will be broadly applicable to other viral infections," says Gewirtz. He and his colleagues are now testing whether the combination allows to withstand a range of mouse viruses, there including norovirus, a gastrointestinal pathogen known to cause outbreaks on cruise ships.
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