Researchers at the University of California San Diego School of Medicine have provided a molecular basis to understand the "hygiene hypothesis," the theory suggesting that the lack of childhood exposure to infectious agents and microorganisms decreases an individual's susceptibility to disease. The research may help scientists devise new therapeutic approaches for inflammatory skin diseases and related skin care.
The researchers, led by post-doctoral fellow Yu Ping Lai, illustrated that bacteria on the skin's surface triggers a pathway that prevents excessive inflammation after injury, which has uncovered elements of the wound repair response. The study was conducted on mice and in human cell cultures and was published in the online edition of Nature Medicine on Nov. 22, 2009.
According to the university press release, staphylococcal bacterial species are present in the skin's normal microflora, and while they induce an inflammatory response when introduced below the skin's surface, they do not initiate inflammation when present on the epidermis.
Lai and fellow researchers revealed a previously unknown mechanism by which a product of staphylococci inhibits skin inflammation. Such inhibition is mediated by a molecule called staphylococcal lipoteichoic acid (LTA), which reportedly acts on keratinocytes. The researchers also found that Toll-like receptor 3 (TLR3) activation is required for normal inflammation after skin injury. Conversely, the inflammation triggered by RLR3 is modulated with staphylococcal LTA.
Richard L. Gallo, MD, PhD, professor of medicine and pediatrics, chief of UCSD’s Division of Dermatology, said in the press release, "To our knowledge, these findings show for the first time that the skin epithelium requires TLR3 for normal inflammation after wounding and that the microflora helps to modulate this response.”
Additional contributors to the paper include: Yuping Lai, Anna Di Nardo, Teruaki Nakatsuji, Anna L Cogen, Chun-Ming Huang and Katherine A. Radek, UCSD Division of Dermatology and the VA San Diego Healthcare System; Anke Leichtle and Allen F. Ryan, UCSD Department of Surgery/Otolaryngology and the VA San Diego Healthcare System; Yan Yang and Zi-Rong Wu, School of Life Science, East China Normal University, Shanghai; Lora V Hooper, Howard Hughes Medical Institute and University of Texas Southwestern Medical Center, Dallas; and Richard R Schmidt and Sonja von Aulock, University of Konstanz, Germany.
The study was funded by grants from the National Institutes of Health, and a US Veterans Administration Merit Award.