How our immune system backfires and allows bacteria like Salmonella to grow

February 6, 2014

Our immune system wages an internal battle every day to protect us against a broad range of infections. However, researchers have found that our immune response can sometimes make us vulnerable to the very bacteria it is supposed to protect us from. A study published by Cell Press on February 6th in the journal Immunity reveals that the immune protein interleukin-22 (IL-22) actually enhances the growth of dangerous bacteria, like Salmonella, which causes food poisoning, and curbs the growth of healthy bacteria commonly found in the gut. The findings suggest that a supposedly protective immune response actually aids the growth of a gut pathogen by suppressing the growth of its closest competitors.

"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," says senior study author Manuela Raffatellu of the University of California, Irvine. "Our findings have important implications for the development of treatment strategies against pathogens that can resist interleukin-22-induced responses."

To protect against disease-causing pathogens, IL-22 triggers the production of antimicrobial proteins that sequester metal ions such as iron, zinc, and manganese from microbes, starving them of these essential nutrients. But until now, it has been unclear how pathogens such as Salmonella escape IL-22's defenses.

To address this question, Raffatellu and her team first infected normal mice, and mice genetically engineered to lack IL-22, with Salmonella. Whereas Salmonella outcompeted the common gut bacterium Escherichia coli (E. coli) in normal mice, the reverse was true for mice lacking IL-22. These findings suggest that IL-22 activity reduced the E. coli population, tipping the balance of gut microbes in favor of Salmonella.

The researchers then simultaneously infected the mice with normal Salmonella as well as mutant Salmonella strains lacking cell membrane proteins for absorbing iron and zinc from the environment. Normal Salmonella strongly outcompeted these mutant strains in normal mice, but this competitive advantage was reduced in mice lacking IL-22. These findings suggest that Salmonella relies on alternative pathways to overcome IL-22's defenses and acquire essential metal ion nutrients.

Even though IL-22 does not protect against all pathogens, the protein still plays a crucial role in controlling the spread of some harmful microbes. "Blocking interleukin-22 during infection would be too detrimental to the host, 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," Raffatellu says.

Explore further: Probiotic bacterium lessens severity of Salmonella infections by hoarding iron

More information: Immunity, Behnsen et al.: "The Cytokine IL-22 Promotes Pathogen Colonization by Suppressing Related Commensal Bacteria."

Related Stories

How to achieve a well-balanced gut

August 8, 2013

Creating an environment that nurtures the trillions of beneficial microbes in our gut and, at the same time, protects us against invasion by food-borne pathogens is a challenge. A study published on August 8 in PLOS Pathogens ...

Salmonella jams signals from bacteria-fighting mast cells

December 12, 2013

A protein in Salmonella inactivates mast cells—critical players in the body's fight against bacteria and other pathogens—rendering them unable to protect against bacterial spread in the body, according to researchers ...

Typhoid Fever: A race against time

January 16, 2014

The life-threatening disease typhoid fever results from the ongoing battle between the bacterial pathogen Salmonella and the immune cells of the body. Prof. Dirk Bumann's research group at the Biozentrum of the University ...

Salmonella infection mitigates asthma

January 23, 2014

Researchers from Germany have identified the mechanism by which Salmonella infections can reduce the incidence of asthma in mice. The research, which appears ahead of print in the journal Infection and Immunity, opens up ...

Recommended for you

Snapshot turns T cell immunology on its head

October 6, 2015

Challenging a universally accepted, longstanding consensus in the field of immunity requires hard evidence. New research from the Australian Research Council Centre of excellence in advanced Molecular imaging has shown the ...

Four gut bacteria decrease asthma risk in infants

September 30, 2015

New research by scientists at UBC and BC Children's Hospital finds that infants can be protected from getting asthma if they acquire four types of gut bacteria by three months of age. More than 300 families from across Canada ...

Flu infection reveals many paths to immune response

September 28, 2015

A new study of influenza infection in an animal model broadens understanding of how the immune system responds to flu virus, showing that the process is more dynamic than usually described, engaging a broader array of biological ...

Immune cells may help fight against obesity

September 15, 2015

While a healthy lifestyle and "good genes" are known to help prevent obesity, new research published on September 15 in Immunity indicates that certain aspects of the immune system may also play an important role. In the ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.