A new target for the treatment of bacterial infections

Researchers at Lund University have identified a new therapeutic target for the treatment of bacterial infections that regulates the immune response.

The scientists found an “off” switch for destructive inflammation in infected kidneys that does not impair the anti-bacterial defence.

The challenge is to strengthen the good, antibacterial defence without causing tissue damage. Inflammation accompanies most infections and symptoms like fever and pain are the price to pay for an effective defence. 

“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’’ says Lund University Professor Catharina Svanborg. “We have also identified genetic variants in susceptible patients that support this concept.”

Irf7-/- mice were protected from infection

Using mice lacking the closely related transcription factors IRF-3 or IRF-7, the researchers were surprised to find that IRF-3 and IRF-7 control different facets of the immune response to kidney infection and that this determines the susceptibility to acute pyelonephritis, which is a severe, potentially life-threatening bacterial infection of the urinary tract.

In contrast to mice lacking IRF-3, which became very ill, Irf7-/- mice were protected from infection and chronic inflammation, suggesting that suppression of Irf7 might be beneficial.

“Based on these findings identifying Irf7 as an immunotherapeutic target. we used siRNA therapy to silence Irf7 and were able to demonstrate protection in susceptible mice,” says Manoj Puthia, researcher at Lund University.

Infections remain the major cause of the deaths worldwide, especially in developing and poorly developed areas. While antibiotics have greatly reduced illness and mortality, many pathogens have developed resistance and we are facing a global crisis.

You can find out more about antibiotic resistance in our infographic.