Monday November 23 2009
“Children should be allowed to play in the dirt because being too clean can impair the skin’s ability to heal itself,” The Daily Telegraph reported. It said scientists have found that common bacteria on the skin’s surface can “dampen down overactive immune responses, which can lead to rashes or cause cuts and bruises to become swollen and painful”.
This news report is based on research in human skin cells and mice. Researchers found that some non-harmful bacteria that live on the skin play an important role in regulating inflammation. These intriguing findings improve our understanding of the complex reactions that occur when cells are infected or injured.
While the newspaper suggests that the findings are directly relevant to children’s health, this was not investigated by the researchers, though they did suggest their results may have some application in the management of inflammatory skin disorders. At this early stage, however, this is speculation and much more research is needed.
Where did the story come from?
The study was carried out by Dr Yuping Lai and colleagues from the University of California and other academic institutions across the USA. The research was funded by the National Institutes of Health and was published in the peer-reviewed medical journal Nature Medicine.
The Daily Telegraph has given a good report of the research, although the focus on children’s health may lead readers to misinterpret the study’s methods. This was laboratory research and included some studies in live mice in which injury was induced.
The findings pave the way for future studies of these complex chemical responses in humans, particularly those with inflammatory skin disorders.
What kind of research was this?
This laboratory study was carried out in mice and human tissue. It investigated whether chemicals produced by the bacteria Staphylococcus epidermidis could inhibit skin inflammation.
In a normal immune response to infection or injury, there needs to be a balance between rapidly responding to the immune challenge (which involves some inflammation) and unnecessary inflammation. S. epidermidis is commonly present on the skin and in most people does not cause disease. In people with weakened immune systems, these bacteria can sometimes cause illness.
The researchers state that finding out how such bacteria exist on the skin without causing inflammatory responses could help them understand whether these bacteria have a role in immune responses in general.
What did the research involve?
The researchers treated human skin cells with a range of chemicals that are involved in the inflammatory response. They found that a chemical called poly(I:C) initiated the greatest inflammatory response. They then pre-treated some skin cells with a chemical produced by S. epidermidis to see whether it had any effect on the inflammation reactions that poly(I:C) induced.
Similar experiments were repeated in live mice, where patches on the ears were pre-treated with the bacterial by-product and then exposed to poly(I:C). The cells’ responses when exposed to other inflammation-inducing chemicals (lipopolysaccharide or phorbol 12-myristate 13-acetate) were also assessed.
The researchers then analysed whether other staphylococcal strains produced this bacterial by-product and if it had a similar effect on inflammatory processes.
The second set of experiments investigated how this bacterial by-product works. To study this, the researchers induced injury in mice that were genetically modified to be missing certain receptors in their cells (called toll-like receptors 3 or TLR3). These receptors are involved in initiating an immune response.
The researchers then assessed the effects of pre-treatment with S. epidermidis in these mice compared with the response in normal mice. Several other experiments explored in more depth TLR3 and inflammation, and how the substances produced by S. epidermidis can prevent this.
What were the basic results?
Pre-treatment of cells with the bacterial by-product (both in culture and in live mice) reduced the inflammatory response caused by poly(I:C). The researchers say this shows that “a product of S. epidermidis functions as a selected suppressor” of the inflammation induced by poly(I:C). It does this ultimately by inhibiting certain receptors called TLR3. They say a range of staphylococcal bacteria produce this by-product.
Pre-treating mice that were genetically modified to lack the TLR3 receptors with the chemical produced by S. epidermidis did not reduce inflammation, confirming that the TLR3 receptors are the target of the chemical. Other TLR receptors (TLR2) were also found to be important.
The chemical that suppressed inflammation in the skin cells was identified as Lipoteichoic acid (LTA), a major component in the cell wall of these types of bacteria. These LTAs had an opposite effect (i.e. they induced inflammatory responses) on other immune cells called macrophages, monocytes and mast cells.
How did the researchers interpret the results?
The researchers say that this study confirms the important role of TLR3 receptors in detecting injury to the skin and that LTAs produced by certain staphylococcal bacteria can inhibit the inflammatory response. They say that the skin is frequently exposed to the LTAs produced by bacteria and that S. epidermidis “may benefit the host by dampening unwanted inflammation”.
This laboratory study sheds light on some of the complex processes involved in the skin’s response to injury. Inflammation is an important response to immune challenges, such as infection and injury, but skin conditions such as psoriasis and eczema are associated with hyperinflammatory reactions (excessive inflammation).
This research suggests that bacteria such as S. epidermidis play an important role in regulating the inflammatory response. The researchers speculate that chemicals produced by this type of bacteria may moderate inflammation from injury and control inflammatory skin disorders. They also highlight the crucial point that any treatment that reduces the detrimental effects of inflammation would have to do so without increasing the risk of wound infection. This balance has yet to be established.
Despite the news reports, this study did not investigate how playing in the dirt might affect children’s immune systems. This interpretation is not surprising and there are theories suggesting that a lack of exposure to some germs early in life can adversely affect the immune system. However, this study was in the laboratory and it is too soon to say that the findings apply directly to children.
This is interesting research that will lead to further work in humans. Until the role of these chemicals has been studied further, the direct relevance to healthy adults or children or for treatment of people with inflammatory skin disorders is unclear.