Salmonella Disables Bacteria-Fighting Mast Cells During Invasion
A protein in Salmonella inactivates mast cells, rendering them unable to protect against bacterial invaders, according to a new study.
AsianScientist (Dec. 17, 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 invaders, according to a new study.
The study, conducted by researchers at Duke Medicine and Duke-NUS Graduate Medical School (Duke-NUS), was published in the journal Immunity.
“Ever since mast cells were discovered to be critical mobilizers of the body’s powerful immune system, it has always been suspected that certain pathogens would have evolved mechanisms directed at undermining this cell,” said senior study author Soman Abraham, professor of emerging infectious diseases at Duke-NUS.
Salmonella bacteria are a leading cause of foodborne illness. While most individuals infected with Salmonella recover quickly, the infection can cause serious illness or even death, particularly among those with weakened immune systems. Salmonella is also becoming increasingly resistant to antibiotic treatment, leading researchers to develop vaccines to try and prevent the bacterial infection.
Studies have shown that Salmonella can rapidly invade the body’s cells and hinder the immune system from mounting responses against future infections by impeding the actions of specific immune cells or targeting the lymph nodes. The rapid spread of Salmonella after breaching the gut barrier, however, suggests a more immediate mechanism for subverting the immune system.
An important component of the immune system is the mast cell, a distinct type of immune cell that initiates an early response to combat and clear invading pathogens. Mast cells are located in large numbers in the skin, gut, lung and bladder lining, which are common sites for pathogens to enter and attack the body.
Upon encountering invading bacteria or viruses, mast cells release large amounts of chemical signals, which recruit various pathogen-clearing immune cells from the blood to the site of infection. However, Salmonella has been shown to be an exception, as mast cells do not clear the bacteria.
To learn how Salmonella handicaps mast cells, Abraham and his colleagues studied Salmonella infection in mice. They found that when mice were exposed to Salmonella via injection or oral administration, a protein called Salmonella protein tyrosine phosphatase (SptP) shut down the mast cells’ ability to release chemical signals without affecting other cellular functions. As a result of the mast cells being unable to call for help, immune cells were not recruited to the infection site, allowing Salmonella to multiply and spread unchecked.
In another experiment, the researchers administered SptP to mice infected with E. coli, a relatively innocuous type of bacteria. With SptP suppressing the mast cells, the bacteria was able to spread inside the mouse just as quickly as Salmonella, suggesting that inactivating mast cells is a key determinant in the spread of pathogens.
The researchers also found that Yersinia pestis, the pathogen responsible for plague, expressed an SptP-like protein that also suppressed mast cells. They now think that the spread of plague bacteria in the body may also involve mast cell suppression.
“The current vaccines against Salmonella are largely ineffective and short lived,” Abraham said. “Our discovery of the virulent properties of SptP raises the possibility of using this information to evoke effective and long-lived protection against Salmonella infection.”
Source: National University of Singapore; Photo: NIAID/Flickr/CC.
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