The study, conducted by researchers from the La Jolla Institute for Allergy & Immunology, is published in the journal Nature.
Lead researcher of the study, Mitchell Kronenberg, Ph.D., La Jolla Institute's president and chief scientific office, explained:
"We've found that a certain 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 our bodies through the lining of our respiratory or intestinal tracts.
We discovered that 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."
The researchers state that their finding will help in the development of new treatments or vaccines against bacterial infections.
Dr. Kronenberg said:
"People knew that epithelial cells protect the body's mucosal borders from infection. But what wasn't known was that HVEM is critically important in turning on the epithelial cell anti-bacterial response. We found that HVEN 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 couldn't withstand the infection."
Richard S. Blumberg, M.D., a professor of medicine at Harvard Medical School and chief of the division of Gastroenteroogy, Hepatology and Endoscopy at Brigham and Women's Hospital, said that the discovery is vital on many levels.
"It is of great biological interest because it shows how this very novel pathway has an important role to play in the management of infections at the epithelial boundaries, which is the entry point for the vast majority of infectious disease.
At the most fundamental levels, it gives us new insights into the way in which our host immune response engages and enables protection mechanisms at the portal of entry. From a therapeutic standpoint, better understanding of these pathways will enable researchers to explore ways to therapeutically manipulate the immune response to prevent and eradicate infectious pathogens at these critical body sites."
Although the researchers focused on E. coli and pneumococcus, the HVEM mechanism is likely involved in protecting the body from other bacteria and microorganisms. HVEM (herpes virus entry mediator) is a protein that herpes virus uses to penetrate cells.
For the study, the team genetically engineered mice to not have HVEM and found that they were considerably more susceptible to infection when exposed to pneumococcus or a mouse pathogen similar to E. coli.
Dr. Kronenberg explained: "It is striking how similar the responses in the lung and the intestine were. 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."
In an associated comment, Victor Nizet, M.D., a professor of Pediatrics and Pharmaceutical Sciences at the University of California, San Diego, said: "In the present era of ever increasing antibiotic resistance, innovative approaches to treatment of bacterial infections are urgently needed. These importantly include new approaches to strengthen immune resistance to infection, and the discovery by the La Jolla Institute scientists reveals HVEM as a candidate drug target with relevance to multiple pathogens and multiple sites of infection."
According to the World Health Organization, pneumococcus is the most prevalent cause of meningitis and bacterial pneumonia in children. Since the introduction of a pneumococcal vaccine in 2000, the number of children in the U.S. infected with the bacteria has decreased significantly. However, the bacteria continues to be a significant problem among children under the age of two, the elderly and throughout the developing world.
Although the majority of E. coli strains are harmless, some can be lethal. E. coli enters the food supply via contamination. While the majority of people develop mild symptoms, some develop severe complications that can result in renal failure and death.
In 2011, more than 4,000 people were sickened by E. coli due to an outbreak centered in Germany. The outbreak, which was traced to contaminated bean sprouts, killed 50 people in 15 countries.
La Jolla Institute scientists Hilde Cheroutre, Jr-Wen Shui, Alexandre Larange, Gisen Kim, Jose-Luis Vela and Sonja Zahner also contributed to this paper. The research was supported by funding from the National Institutes of Health.
Written by Grace Rattue