With antibiotic resistance on the rise, health experts are increasingly expressing alarm about the future of medicine. One potential path is suggested by a recent study, published in the journal Science Translational Medicine, in which researchers from Lund University successfully induced the immune systems of mice to fight off a kidney infection without the use of any antibiotics.
The study focused on “innate immunity,” which is the body’s first line of defense and can be used even against pathogens that have never been encountered before. Prior research has shown that innate immune responses typically contain two major components: an antibacterial defense that actively destroys the invaders, and an inflammatory response that helps create an environment hostile to the pathogen and favorable to immune agents and healing processes.
Inflammation can be damaging to tissues, however, and may cause further health problems if it gets out of hand.
“So the question has been: Can you find a way of treating infections by stopping the bad part of the immune defense and still keep the antibacterial defense?” researcher Catharina Svanborg said. “This is what we have done in our model.”
Focusing the immune response
The study was conducted on mice infected with a bacterium that can cause severe kidney infections in humans, particularly in children. In these infections, the inflammatory response can get out of control and sometimes even cause organ failure.
To their surprise, the researchers discovered that two closely related transcription factors (chemicals that help regulate DNA expression) controlled the two parts of the innate immune response: IRF-3 activated the antibacterial response, and IRF-7 activated the inflammatory response. When researchers knocked out the former factor in infected mice, the mice became very ill. When they knocked out IRF-7, however, the mice’s immune systems seemed to kick into high gear, and they recovered significantly better than control mice.
“It is a surprise because this technology has not been used in this way to treat infections,” Svanborg said. “So, it was an unexpected finding… but it was a logical step to take.”
She suggested that some genetic susceptibility to disease may come from overactive IRF-7.
“We knew that specific transcription factors regulate innate immune responses to bacterial infection and that the outcome of infection be beneficial or destructive, depending on how these regulators work” she said.
Immune system still the best defense
The researchers are now planning to see whether the same process can also boost immunity against other pathogens.
“The picture is the same for all these different categories, and conceptually, what we’ve done is to say: Instead of killing the bacteria directly, we are harnessing the immune system in such a way that the tissue damage is suppressed and the symptoms are suppressed,” Svanborg said.
Svanborg said that, given rising rates of antibiotic resistance, techniques such as this may soon be necessary to treat certain illnesses.
Infection is still the leading cause of death globally, particularly in less wealthy countries. Even in wealthy countries, the rise of drug-resistant superbugs is placing the entire medical system in peril.
“The rise of antibiotic resistance is a global health crisis,” said World Health Organization head Margaret Chan last year. “More and more governments recognize (it is) one of the greatest threats to health today.”
Chan warned that, if steps are not taken to stem the rapid revolution of antibiotic resistance, it could mean “the end of modern medicine as we know it,” and “a post-antibiotic era, in which common infections will once again kill.”
Antibiotics are not just used to treat infections; they are the foundation upon which the modern medical system is built. Many now-routine procedures such as surgeries, chemotherapy and care of premature infants cannot be performed without reliable antibiotics.
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