Our guts are home to over a 100 trillion bacteria that help digestion, prevent inflammatory bowel disease (IBS) and protect us from invaders, such as harmful bacteria. To keep pathogens at bay without destroying ‘good’ bacteria, there is a subset of specialised cells in the gut epithelium that act as sentinels. These so called ‘M cells' engulf and rapidly transport large particles from the gut lumen to the underlying lymphoid tissue, where they are recognised and sorted by immune cells. This ability to sample foreign agents, much like a police border control, is critical to trigger immune responses against disease-causing pathogens, while maintaining a healthy gut microbe balance.
|Uncooked meat is one of the most common sources of Salmonella infection.|
However, the unique feature of M cells to efficiently carry particules across the gut wall is a double-edged sword, as pathogens such as bacteria and virus can use them as free tickets to enter the bloodstream and invade other regions of the body. In fact, some pathogenic bacteria can even increase the number of M cells to boost their transport across the gut epithelium, but exactly how they do this is not understood. Arvin Mahajan and colleagues from the University of Edinburgh tackled this question by infecting bovine cultured gut epithelial cells with Salmonella, in a recent Cell Host & Microbe study.
Salmonella enterica serovar Thyphimurium (S. Thyphimurium) are pathogenic bacteria found in raw eggs, uncooked meat, some vegetables and reptiles (recent Salmonella outbreaks were linked to pet turtles). S. Thyphimurium infection causes diarrhoea, abdominal cramps, vomiting and fever. Most people clear the infection within a week without needing any treatment, but for young children, older adults and people with weakened immune systems, the infection can sometimes be fatal because it spreads from the gut into vital organs, such as the kidneys or liver. S. Typhimurium can invade different cell types to colonise their host, but they preferentially take a shortcut by making more M cells and hitchhiking on them to cross the gut barrier.
|Salmonella Thyphimurium (red) invading cultured human epithelia cells.|
(Credit: Wikipedia Commons)
But how do Salmonella induce more M cells? Scientists have long been arguing whether bacteria-induced M cells are newly born cells, or instead come from epithelial cells that somehow change their identity. Mahajan’s team first showed that S. Typhimurium induce a rise in M cell numbers just 90 minutes after infection, which ruled out the first hypothesis, because cells normally take 3 to 4 days to fully mature. Next, the scientists went on a fishing expedition for the bacterial molecule that causes the cell transformation. They infected the cultured bovine gut cells with S. Typhimurium mutant strains, each lacking a different molecule, and found that the bacterial protein SopB is essential to induce more M cells, and these results were confirmed in the mouse small intestine. Finally, the researchers figured out the chain of cellular events triggered by SopB that causes the epithelial to M cell transformation.
By showing that with a single virulent factor (SopB) Salmonella transform gut epithelial cells into gateways, Mohajan and colleagues have revealed yet another clever strategy used by pathogenic bacteria to invade and colonise their host.
Tahoun A., Mahajan S., Paxton E., Malterer G., Donaldson D., Wang D., Tan A., Gillespie T., O’Shea M. & Roe A. & (2012). Salmonella Transforms Follicle-Associated Epithelial Cells into M Cells to Promote Intestinal Invasion, Cell Host & Microbe, 12 (5) 645-656. DOI: 10.1016/j.chom.2012.10.009
A shorter version of this article was published in Lab Times on the 7-02-13. You can read it here.