We all know by now that eating undercooked or raw poultry can result in food poisoning, due to the bacteria Salmonella. But less clear to scientists was how exactly the bacteria overrode the host’s own bacteria, which were thought to help fend off these very intruders. Now, thanks to a new study from the University of California, Irvine, researchers have discovered the answer.

It turns out there’s a sort of Benedict Arnold of immune system bacteria. It’s called interleukin-22 (IL-22). A protein responsible for controlling cellular inflammatory responses, IL-22 plays a key role in defending the body against incoming infection. However, in the presence of IL-22, the protein does an about-face and actually aids the invading bacteria in its spread throughout the host, the team found. The discovery could prove supremely useful for developing therapies to resolve a Salmonella infection.

"Surprisingly, we found that interleukin-22 not only fell short in protecting the host against the spread of Salmonella, but it was also actually beneficial to these harmful bacteria," senior study author Manuela Raffatellu, of UC Irvine, said in a statement. "Our findings have important implications for the development of treatment strategies against pathogens that can resist interleukin-22-induced responses."

Basically, IL-22 works by shutting down the essential pathways that intruding bacteria use to harm the body. It jumpstarts the production of antimicrobial proteins that seize metal ions such as iron, zinc, and manganese from microbes, robbing the microbes of necessary nutrients. But Salmonella, the team found, doesn’t play by these rules.  

To better understand the relationship between good and bad bacteria, the team introduced normal mice, and mice genetically engineered to lack IL-22, with Salmonella. The observed Salmonella outcompeted the common gut bacterium Escherichia coli (E. coli) in normal mice, but mice that didn’t have IL-22 weren’t able to fend off either. This signaled that IL-22 was critical in reducing E. coli populations, tipping the gut microbe balance in favor of Salmonella.

Then, they introduced both a normal strain and a mutant strain of Salmonella, which lacked the membrane necessary to absorb iron and zinc, to normal mice and those lacking IL-22. They observed that while the normal Salmonella did a better job at infecting normal mice than the mutant strain did, that effect was reduced when mice lacked IL-22. This implied an alternate pathway was at work, because IL-22 had become irrelevant in stopping the weakened mutant strain.

Despite Salmonella’s standing as one of the most prominent strains of bacteria in the world, IL-22 remains crucial for a range of duties — primarily in the defense against other bacteria spreading throughout the body. So the solution can’t be just to get rid of it. Researchers believe their new understanding of how Salmonella interacts with IL-22 can also open new doors for understanding how other pathogens work in the same way as the foodborne illness.

"Blocking interleukin-22 during infection would be too detrimental to the host,” Raffetellu concluded, “so a more promising therapeutic strategy would be to specifically target the alternative pathways used by Salmonella and potentially other pathogens to evade interleukin-22's defenses.”


Sources: O’Donnell H, Pham O, Li L, et al. Toll-like Receptor and Inflammasome Signals Converge to Amplify the Innate Bactericidal Capacity of T Helper 1 Cells. Immunity. 2014.