Regarding animal models of the immune system, laboratory mice as the profane own version of a song ?; they are still pretty good, but they can not capture the texture of real life. Unlike wild rodents, laboratory mice are bred, raised, and lodged in essentially sterile environments. It experimented with the easiest to reproduce and control, but it also raised serious concerns about whether or not they are realistic models for humans. Now, two new studies, researchers have proposed a way to "dirty" these mice, although some fear that the work could jeopardize future studies.
"I think these very, very important are studies," says immunologist John Wherry at the University of Pennsylvania, who was not part of the work. "They have a lot of impact on how we think of a chronic infection and global health."
The first of the new studies, published today in Nature David Masopust immunologist at the University of Minnesota, Twin Cities, Minneapolis and his team set out to create mice laboratory whose immune system more like their wild counterparts. They did this by obtaining mouse in pet stores, which have no sterile precautions facilities reserved for laboratory mice, and place them in a cage with laboratory mice. Before cohabitation, laboratory mouse has a low number and variety of memory T cells, which are specialized in the fight against a variety of foreign invaders. Their "immune profile" closely resemble that of a newborn, probably because they rarely have to deal with infections. "[Lab mice] had a very privileged life," said Masopust. "We do not live like that."
Things changed radically after 2 months with the pet mouse. Twenty-two percent laboratory mice died, but those who survived showed profound changes in their immune system. exposure to increased pathogen various components of the immune system in the blood, especially cell subsets T moving specialized immune profile closer to that of an adult human. the tests for common pathogens mice showed that laboratory mice were exposed to viruses, bacteria and parasites worm. cohousing has also changed the way the mice responded to new infections: After mixing with dirty mice, laboratory mice showed 10,000 times in their immune response against a bacterium known as Listeria monocytogenes -a reaction tied with animals mouse store themselves.
Masopust believes the experience has produced mice with immune systems more realistic kind of animal you would need, he said, to test more precisely the power and safety of new drugs and vaccines. He says that in the future, researchers could expose laboratory mice a mixture of pathogens similar to what humans might experience to get a better idea of what this directory is for the immune system in general. In a perfect world, researchers could adapt this directory to match the pathogens of certain parts of the world as well.
And indeed, scientists are studying exactly the idea. In the second study, published today in Cell Host & Microbe , viral immunologist Skip Virgin of Washington University in St. Louis, Missouri and his team infected laboratory mice with herpes and influenza virus as well as intestinal worms to trace how rodents responded to a vaccine against yellow fever. "We are interested to see if we could change and, at least in theory, improve the mouse model by its exposure to more normal environmental agents," says Virgin. These pathogens were selected because they represent common infections in many parts of the world; if their presence affects how animals react to the vaccine could help explain why some vaccines seem to work better in some populations than others.
Initially, immune responses to the vaccine against yellow fever were similar between mouse and a standard laboratory co-infected with other pathogens group, but after 34 days, the group co -infecté showed signs of a reduced immune response to the vaccine, as shown by a decrease in the amount of antibodies directed against the vaccine components present in the blood of rodents. Analyses of the DNA in the blood of mice have also shown that gene expression differed between the two groups. The researchers observed changes in the fundamental genetic activation of T cells, cell death and immune response to signaling molecules, indicating that co-infection with other common pathogens modifies the immune system at the genetic level .
"[Masopust] showed that the natural state of animals is very different in nature or a pet store in a [lab]," said Mary. "We have shown that in controlled conditions, you can make substantially similar changes taking this very own mouse and giving it a range of infections. "
Exploiting this knowledge to create mice populations that closely mimic human immune systems is still far away, though. one of the biggest challenges will be to do it in a way that does not ruin the many benefits of laboratory mice. Imperfect as they may be, laboratory mice have shown an excellent model for the man in countless scientific experiments. Their sterile environment and the blank slate of immune system ensures that all scientists are working with the same models. Introducing changes to the immune system must be done in a very careful and calculated manner if it works all, Virgin said.
Wherry is also cautious, noting that apart from the issue of reproducibility, it will also be expensive and time consuming to create and house mouse populations with the desired immune profiles. "I think we'll see it used selectively in certain areas," he said. "It would be very difficult to do consistently and apply at all levels." Despite the difficulties, Wherry says he can envision a future in which scientists can select from a library of mice with defined immune profiles that reflect different human populations.
"That's the dream," Virgin said.
* Correction, April 21, 9:03 a.m. The original version of this article mentioned mice and rats. The experiments were carried out on mice only.
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