Scientists identify critical cell in fighting E. coli infection
Despite ongoing public health efforts, E. coli outbreaks continue to infiltrate the food supply, annually causing significant sickness and death throughout the world. But the research community is gaining ground. In a major finding, published today in the scientific journal Nature, researchers from the La Jolla Institute for Allergy & Immunology have discovered a molecule's previously unknown role in fighting off E. coli and other bacterial infections, a discovery that could lead to new ways to protect people from these dangerous microorganisms.
"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," said Mitchell Kronenberg, Ph.D., La Jolla Institute's president and chief scientific officer, who led the research team. "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," said Dr. Kronenberg, adding that he is hopeful the discovery will advance efforts toward developing new treatments or vaccines against bacterial infections.
"People knew that epithelial cells protect the body's mucosal borders from infection," said Dr. Kronenberg. "But what wasn't known was that HVEM is critically important in turning on the epithelial cell anti-bacterial response." Epithelial cells line the body's 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 couldn't withstand the infection," said Dr. Kronenberg.
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, called the finding important 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 diseases," he said. "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 that 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."
While the study, "HVEM signaling at mucosal barriers provides host defense against pathogenic bacteria," focused on E. coli and pneumococcus (also known as Streptococcus pneumoniae), Dr. Kronenberg said the HVEM mechanism is likely involved in protecting the body from many other dangerous bacteria and other microorganisms. In fact, HVEM stands for herpes virus entry mediator, and it is a protein that herpes virus uses to enter cells.
In the study, the researchers used mice genetically engineered not to have HVEM. When these 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," said Dr. Kronenberg. "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 the present era of ever increasing antibiotic resistance, innovative approaches to treatment of bacterial infections are urgently needed," commented Victor Nizet, M.D., a professor of Pediatrics and Pharmaceutical Sciences at the University of California San Diego. "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."
Pneumococcus is the most common cause of bacterial pneumonia and meningitis in children. According to the World Health Organization, pneumonia is the single largest cause of death in children worldwide, annually killing an estimated 1.4 million children under the age of five. While cases among U.S. children have declined significantly due to the introduction of a pneumococcal vaccine in 2000, the bacteria remains a significant problem, particularly among U.S. children under two years, the elderly and throughout the developing world.
Escherichia coli (abbreviated as E. coli) are a large and diverse family of bacteria. Although most strains of E. coli are harmless, some can be deadly. E. coli creeps into the food supply through contamination by tiny (usually invisible) amounts of human or animal feces. Many people may develop mild symptoms, but some suffer severe complications that can lead to kidney failure and death. In 2011, an E. coli outbreak centered in Germany sickened more than 4,000 people, ultimately killing 50 people in 15 countries. The outbreak was eventually traced to contaminated bean sprouts.
Journal reference: Nature
Provided by La Jolla Institute for Allergy and Immunology
- Research discovers novel mechanism for preventing infection via body's mucosal borders Oct 03, 2011 | not rated yet | 0
- Caspase-12: Researcher finds new defense mechanism against intestinal inflammation Mar 12, 2008 | not rated yet | 0
- E. coli bacteria more likely to develop resistance after exposure to low levels of antibiotics Jun 14, 2011 | not rated yet | 0
- TLR1 protein drives immune response to certain food-borne illness in mice Jul 10, 2012 | not rated yet | 0
- Friend or Foe? Scientists Determine How the Intestine Keeps Us Safe From Microbial Invaders Feb 21, 2007 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
How can there be a term called "intestinal metaplasia" of stomach
15 hours ago Hello everyone, Ok Stomach's normal epithelium is simple columnar, now in intestinal type of adenocarcinoma of stomach it undergoes "intestinal...
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
Ratio of Hydrogen of Oxygen in Dessicated Animal Protein
May 13, 2013 As an experiment, for the past few months I've been consuming at least one portion of Jell-O or unflavored Knox gelatin per day. I'm 64, in very...
Alcohol and acetaminophen
May 13, 2013 Edit: sorry for the typo in the title , can't edit I looked around on google quite a bit and it's very hard to find precise information on the...
- More from Physics Forums - Medical Sciences
More news stories
Trends in Helicobacter pylori (H. pylori) and smoking explain a significant proportion of the decline of intestinal-type noncardia gastric adenocarcinoma (NCGA) incidence in US men between 1978 and 2008, and are estimated ...
Medical research 4 hours ago | not rated yet | 0
Widely available in pharmacies and health stores, phosphatidylserine is a natural food supplement produced from beef, oysters, and soy. Proven to improve cognition and slow memory loss, it's a popular treatment for older ...
Medical research 9 hours ago | 5 / 5 (1) | 0 |
Researchers at Emory University have identified a protein that stimulates a pair of "orphan receptors" found in the brain, solving a long-standing biological puzzle and possibly leading to future treatments for neurological ...
Medical research 10 hours ago | not rated yet | 0 |
Australian scientists have charted the path of insulin action in cells in precise detail like never before. This provides a comprehensive blueprint for understanding what goes wrong in diabetes.
Medical research 10 hours ago | 4.8 / 5 (4) | 0 |
Researchers at the University of Illinois at Chicago College of Medicine will study gender differences in how the heart uses and stores fat—its main energy source—and how changes in fat metabolism play ...
Medical research 13 hours ago | not rated yet | 0
(Medical Xpress)—Native peoples in regions where cameras are uncommon sometimes react with caution when their picture is taken. The fear that something must have been stolen from them to create the photo ...
10 hours ago | 4 / 5 (4) | 0 |
(Medical Xpress)—Despite spending billions of dollars on research and development, drug companies have been unable to come up with effective treatments for dementia and Alzheimer's Disease (AD). Now, A. ...
8 hours ago | 4.8 / 5 (6) | 0 |
An experimental sleeping pill from US drug company Merck is effective at helping people fall and stay asleep, according to reviewers at the US Food and Drug Administration, which could soon approve the new drug.
4 hours ago | 5 / 5 (1) | 0
Activating an enzyme known to play a role in the anti-aging benefits of calorie restriction delays the loss of brain cells and preserves cognitive function in mice, according to a study published in the May ...
4 hours ago | 5 / 5 (3) | 0 |
A drug commonly used to treat depression and anxiety may improve a stress-related heart condition in people with stable coronary heart disease, according to researchers at Duke Medicine.
5 hours ago | not rated yet | 0 |
Researchers at USC have found that a class of pharmaceuticals can both prevent and treat Alzheimer's Disease in mice.
7 hours ago | 5 / 5 (3) | 0 |