How skin makes out ‘good’ bacteria

CENTENARY INSTITUTE

There are more bacteria living on our skin and in our gut than cells in our body. We need them. But until now, no one knew how the immune system could tell that these bacteria are harmless. Centenary Institute researchers in Sydney have discovered a set of peacekeepers—immune cells in the outer layers of our skin that stop us from attacking friendly bacteria. The work will open the way to new therapeutic options for immune-mediated diseases such as inflammatory bowel disease, of which Australia has some of the world’s highest rates. In a paper published today in the Proceedings of the National Academy of Sciences (PNAS), Professor Barbara Fazekas de St Groth and her team have shown that the immune cells in the outer layer of the skin constantly act as peacekeepers to stop the immune system from reacting the way it usually would. Known as Langerhans cells, they resisted every attempt by the researchers to get them to generate an immune response.  The researchers worked with a group of mice in which only the Langerhans cells could stimulate the immune system. They then activated the Langerhans cells and measured the response. “No matter what we threw at them to get them to activate a long-term immune response, the Langerhans cells always induced immune tolerance,” Prof Fazekas says. This result seems to go against the prevailing wisdom in immunology about the workings of dendritic cells, the class of immune cell to which Langerhans cells belong. Dendritic cells engulf bacteria, viruses or other invaders and put a marker from that invader, known as an antigen, on a protein that can bind to other immune cells. The antigen reprograms passing T cells, the workhorses of the immune system, which then set off a cascade of responses that eventually lead to the destruction of anything displaying that antigen.  However, the Centenary team (which is affiliated with the University of Sydney and RPA Hospital) found Langerhans cells are very different from other dendritic cells: after turning on the helper T cells, they tell them to self-destruct instead. “This is the opposite of what you’d usually expect.  In previous studies of immune cells, if there was a flurry of activity, we assumed it was the start of a long-term immune response,” Prof Fazekas says. However, the immune system is a layered defence­—the next layer of skin has different kinds of dendritic cells, which program on-going responses against bacteria. So if bacteria penetrate deep enough to meet these cells, the immune response will kill them. In inflammatory bowel disease, which afflicts thousands of Australians, the immune system is activated against the gut bacteria, which are usually left alone.  This discovery opens up possible ways to figure out why this disorder occurs and to find treatments to a range of diseases of the immune system. “There is so much we don’t know about the immune system, but sometimes just mimicking what the system does, like we do with vaccines, can work very well,” Prof Fazekas says, “If we do manage to mimic what Langerhans cells do, then we could develop treatments that would precisely tolerise against specific antigens – just like the skin's immune system does now.” Centenary Institute executive director Professor Mathew Vadas says this latest paper comes just weeks after Centenary researcher Patrick Bertolino made the front cover of PNAS for his paper on immune response in the liver. “The Centenary Institute is interested in understanding how the immune system works—these discoveries and others already in the pipeline here are a major step towards that goal,” Prof Vadas says. Editor's Note: Original news release can be found here.

Eat less protein: snack more

THE UNIVERSITY OF SYDNEY

Including enough protein in our diets, rather than simply cutting calories, is the key to curbing appetites and preventing excessive consumption of fats and carbohydrates, a new study from the University of Sydney has found. A multidisciplinary team of researchers has shown that people on a 10 percent protein diet will consume more snacks between meals and eat significantly more calories overall compared to those on a 15 percent protein diet. The results, published in the online journal PLoS ONE, represent the first scientifically supported evidence that dietary protein plays an important role in appetite and total food consumption in humans, and are an important step in addressing the global obesity epidemic. "Humans have a particularly strong appetite for protein, and when the proportion of protein in the diet is low, this appetite can drive excess energy intake," said lead author Dr. Alison Gosby, who conducted the study with Professor Steve Simpson from the School of Biological Sciences. "Our findings have considerable implications for body weight management in the current nutritional environment, where foods rich in fat and carbohydrates are cheap, palatable, and available to an extent unprecedented in our history." Protein is the driving force for appetite in many animals, according to Professor Steve Simpson, a world leader in nutrition. The 'protein-leverage' hypothesis, first proposed by Steve Simpson and co-author David Raubenheimer, proposes that animals have a fixed protein target, which they will defend at the expense of other nutrients. "Our previous work on slime moulds, insects, fish, birds, rodents, mink, cats and monkeys has shown that animals have separate appetites for protein, fat and carbohydrate. Interestingly, if protein in the diet is diluted, even by a small amount by extra fat and carbohydrate, the appetite for protein dominates and they will keep eating in an attempt to attain their target level of protein," he says. Although it has previously been suggested that protein content plays an important role in determining overall energy intake in humans, and is therefore linked to obesity, until now experimental verification has been lacking. In their new study, Dr Gosby and Professor Simpson wanted to test the 'protein-leverage' effect in humans. The researchers created three menus that represented low (10 percent), intermediate (15 percent) and high (25 percent) protein, based on data from the World Health Organization recommending people eat 15 percent protein diets. Except for protein, the three diets were identical in all other factors such as appearance, palatability, variety and availability. The researchers then took a group of 22 lean people and fed each subject each of the three menus during three separate four-day periods, monitoring energy intake over each four days and hunger ratings on day four. The researchers found subjects who ate a 10 percent protein diet consumed 12 percent more energy over four days than those eating a 15 percent protein diet. Moreover, 70 percent of the increased energy intake on the lower protein diet was attributed to snacking. When the protein content was further increased to 25 percent, however, the researchers observed no change in behavior relative to the 15 percent protein diet. On the fourth day of the trial, however, there was a greater increase in the hunger score between one to two hours after the 10 percent protein breakfast versus the 25 percent protein breakfast. Dr Gosby commented: "This result confirms the 'protein-leverage' effect in humans and importantly, shows counting calories is not enough to manage appetite and body weight. In the western world, where food is abundant, if you reduce your calorie intake but fail to reach your protein target you will find it hard to resist hunger pangs." Professor Simpson says today's western-world diets - where protein is increasingly diluted by fats and carbohydrates - are likely to be causing us to overeat and could be fueling the obesity epidemic. "Our results indicate low protein diets will cause humans to overeat. Tragically in the modern westernised environment there are many factors encouraging us to eat foods that are high in sugars and fat, including reduced cost and increased availability of these foods. Underpinning all this is our ancestral environment in which fat and simple sugars were highly prized, leaving us with a predilection for these foods." Editor's Note: Original news release can be found here.

TOP FIVE QUOTES FOR SUCCESS

Sometimes it takes inspiration to motivate you to make the changes that you want to see in your life. These top 5 quotes make choices, dreams and achievements clear and attainable. Take a tip from these intelligent people and jump-start into the life you want to live today!

Board of Wisdom highlights…

“Too many people go through life waiting for things to happen instead of making them happen!”

-        Sasha Azevedo, Actress (1978 May 20)

“While most are dreaming of success, winners wake up and work hard to achieve it.”

-        Unknown

“There are no shortcuts to any place worth going.”

-        Helen Keller

“The elevator to success is out of order. You’ll have to use the stairs…. One step at a time.”

-        Unknown

“I’ve missed more than 9000 shots in my career. I’ve lost almost 300 games. Twenty-six times, I’ve been trusted to take the game-winning shot and missed. I’ve failed over and over and over again in my life. And that is why I succeed.”

-        Michael Jordan