March 2, 2006
One of the more fascinating issues in oral immunology is why immune cells attack certain microbes but coexist with others. For the so-called gram negative bacteria, the answer seems to lie in a large structural molecule called lipopolysaccharide, or LPS, which interestingly also houses the chain-like chemical endotoxin that can make people sick. Studies show our immune cells have surface proteins called toll-like receptors that recognize gram-negative species by the unique chemical signature of their LPS. Depending upon the bacterium, immune cells can selectively learn to respond strongly or tolerate their endotoxin.
Given the fundamental nature of this interaction to human health, a team of NIDCR grantees has hypothesized that the chronic periodontitis might arise from subtle modifications in the LPS- immune cell interaction. In essence, the immune cells become tricked into tolerating the oral bacteria associated with chronic periodontitis. This occurs by repeated exposure to LPS in dental plaque, which reduces the toll-like receptors that identify the LPS signatures. Thus, by biochemical default, the immune cells become tolerant of these suspicious, endotoxin-bearing bacteria and allow them to invade oral mucosa cells. In the February issue of the journal Infection and Immunity, these grantees add two important pieces of evidence to bolster their hypothesis. They show for the first time that people with chronic periodontitis overproduce a molecule known as SHIP, which plays an important regulatory role in telling immune cells to tolerate an endotoxin. They also determined, based on the reduction of certain toll-like receptors, key oral immune cells isolated from people with chronic periodontitis are in a tolerized state. Taken together, these data suggest a possible biochemical mechanism to target in preventing or treating chronic periodontitis.