Scientists ID Molecule that Fights E. coli

SAN DIEGOScientists have discovered a key molecules role in fighting off E. coli and other bacterial infections, a discovery that could lead to new ways to protect people from dangerous microorganisms, according to a new study published in the journal Nature.

Researchers from the La Jolla Institute for Allergy & Immunology (LIAI) found the molecule, known as HVEM, expressed by the cells lining the surface of the lung and intestine, is critical to protecting the body from E. coli, pneumococcus and other bacterial infections that enter a persons body through the lining of our respiratory or intestinal tracts.

HVEM acts in these cells like a border guard that responds to the presence of invasive bacteria and signals the immune system to send in more troops. Without its involvement as part of the epithelial protective barrier, the body could be overrun by certain disease causing bacteria," said Mitchell Kronenberg, Ph.D., La Jolla Institutes president and chief scientific officer, who led the research team, adding that he is hopeful the discovery will advance efforts toward developing new treatments or vaccines against bacterial infections.

Epithelial cells protect the bodys mucosal borders from infection, but what wasnt known was that HVEM is critically important in turning on the epithelial cell antibacterial response. Epithelial cells line the bodys mucosal borders, which include the mouth, nose, intestines and lungs, and are the most common entry points for infectious pathogens.

We found that HVEM and another receptor (the receptor for IL-22) have to act together in the epithelial cells to trigger immune protection. Without these two receptors acting in concert, the body couldnt withstand the infection," he said.

For the study, researchers used mice genetically engineered not to have HVEM. When the mice were exposed to pneumococcus or a mouse pathogen very similar to E. coli, the HVEM deficiency led to a much greater susceptibility to infection, higher bacterial burdens and significantly compromised the mucosal barrier.

It is striking how similar the responses in the lung and the intestine were," Kronenberg said. The mice without HVEM were unable to respond effectively at either site, and the deficit was not only major but also nearly immediate, within two days of exposure to the microorganisms."