Corporate Banner
Satellite Banner
Scientific Communities
Become a Member | Sign in
Home>News>This Article

Gum Disease Bacteria Selectively Disarm Immune System, Penn Study Finds

Published: Friday, June 13, 2014
Last Updated: Friday, June 13, 2014
Bookmark and Share
New study shows that bacteria responsible for many cases of periodontitis cause dysbiosis.

The human body is comprised of roughly 10 times more bacterial cells than human cells. In healthy people, these bacteria are typically harmless and often helpful, keeping disease-causing microbes at bay. But, when disturbances knock these bacterial populations out of balance, illnesses can arise. Periodontitis, a severe form of gum disease, is one example.

In a new study, University of Pennsylvania researchers show that bacteria responsible for many cases of periodontitis cause this imbalance, known as dysbiosis, with a sophisticated, two-prong manipulation of the human immune system.

Their findings, reported in the journal Cell Host & Microbe, lay out the mechanism, revealing that the periodontal bacterium Porphyromonas gingivalis acts on two molecular pathways to simultaneously block immune cells’ killing ability while preserving the cells’ ability to cause inflammation.

The selective strategy protects “bystander” gum bacteria from immune system clearance, promoting dysbiosis and leading to the bone loss and inflammation that characterizes periodontitis. At the same time, breakdown products produced by inflammation provide essential nutrients that “feed” the dysbiotic microbial community. The result is a vicious cycle in which inflammation and dysbiosis reinforce one another, exacerbating periodontitis.

George Hajishengallis, a professor in the Penn School of Dental Medicine’s Department of Microbiology, was the senior author on the paper, collaborating with co-senior author John Lambris, the Dr. Ralph and Sallie Weaver Professor of Research Medicine in the Department of Pathology and Laboratory Medicine in Penn’s Perelman School of Medicine. Collaborators included Tomoki Maekawa and Toshiharu Abe of Penn Dental Medicine.

Work by Hajishengallis’s group and collaborators had previously identified P. gingivalis as a “keystone pathogen.” Drawing an analogy from the field of ecology, in which a species such as a grizzly bear is thought of as a keystone species because of the influence it has over a number of other species in the community, the idea suggests that, although P. gingivalis may be relatively few in number in the mouth, their presence exerts an outsized pull on the overall microbial ecosystem. Indeed, the team has shown that, although P. gingivalis is responsible for instigating the process that leads to periodontitis, it can’t cause the disease by itself.

“Scientists are beginning to suspect that keystone pathogens might be playing a role in irritable bowel disease, colon cancer and other inflammatory diseases,” Hajishengallis said. “They’re bugs that can’t mediate the disease on their own; they need other, normally non-pathogenic bacteria to cause the inflammation.”

In this study, they wanted to more fully understand the molecules involved in the process by which P. gingivalis caused disease.

“We asked the question, how could bacteria evade killing without shutting off inflammation, which they need to obtain their food,” Hajishengallis said.

The researchers focused on neutrophils, which shoulder the bulk of responsibility of responding to periodontal insults. Based on the findings of previous studies, they examined the role of two protein receptors: C5aR and Toll-like receptor-2, or TLR2.

Inoculating mice with P. gingivalis, they found that animals that lacked either of these receptors as well as animals that were treated with drugs that blocked these receptors had lower levels of bacteria than untreated, normal mice. Blocking either of these receptors on human neutrophils in culture also significantly enhanced the cells’ ability to kill the bacteria. Microscopy revealed that P. gingivalis causes TLR2 and C5aR to physically come together.

“These findings suggest that there is some crosstalk between TLR2 and C5aR,” Hajishengallis said. “Without either one, the bacteria weren’t as effective at colonizing the gums.”

Further experiments in mice and in cultured human neutrophils helped the researchers identify additional elements of how P. gingivalis operates to subvert the immune system. They found that the TLR2-C5aR crosstalk leads to degradation of the protein MyD88, which normally helps clear infection. And in a separate pathway from MyD88, they discovered that P. gingivalis activates the enzyme PI3K through C5aR-TLR2 crosstalk, promoting inflammation and inhibiting neutrophils’ ability to phagocytose, or “eat,” invading bacteria.

Inhibiting the activity of either PI3K or a molecule that acted upstream of PI3K called Mal restored the neutrophils’ ability to clear P. gingivalis from the gums.

“P. gingivalis uses this connection between C5aR and TLR2 to disarm and dissociate the MyD88 pathway, which normally protects the host from infection, from the proinflammatory and immune-evasive pathway mediated by Mal and PI3K,” Hajishengallis said.

Not only does the team’s discovery open up new targets for periodontitis treatment, it also suggests a bacterial strategy that could be at play in other diseases involving dysbiosis.

Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,500+ scientific posters on ePosters
  • More Than 5,200+ scientific videos on LabTube
  • 35 community eNewsletters

Sign In

Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

New Mechanism of Plant RNA Degradation Identified
Researchers have identified a novel mechanism by which RNA is degraded.
Thursday, October 20, 2016
Anti-Inflammatory Drugs Could Strengthen Airway Immunity
Mold toxins can weaken the airways' clearing mechanisms and immunity, but PKC inhibitors showed promise as a treatment.
Thursday, September 29, 2016
Drug Target for Raising Social Interaction in Autism Identified
New mouse model has identified a drug target that could increase social interaction for sufferes of ASD.
Tuesday, September 13, 2016
Case for Liquid Biopsies Builds in Advanced Lung Cancer
Study addresses unmet need for better, non-invasive tests called out in recent "Moonshot" blue ribbon panel report
Tuesday, September 13, 2016
Blinding Disease in Canines and Humans Shares Causative Gene, Pathology
Scientists report that they’ve directly compared the disease course between humans and dogs and found remarkable similarities.
Wednesday, August 31, 2016
LncRNAs Maintain Immune Health
Long non-coding RNAs are key controllers for maintaining immune health when fighting infection or preventing inflammatory disorders.
Friday, August 26, 2016
Designing Drug Delivery Nanocarriers
A team of University of Pennsylvania researchers has developed a computer model that will aid in the design of nanocarriers, microscopic structures used to guide drugs to their targets in the body.
Friday, August 05, 2016
A New Therapy for Autoimmune Diseases
Preclinical study from Penn shows that engineered T cells can selectively target the antibody-producing cells that cause autoimmune disease.
Monday, July 04, 2016
New CAR T Cell Therapy Using Double Target Aimed at Solid Tumors
Researchers at Penn University have described how antibody, carbohydrate combination could apply to range of cancer types.
Friday, July 01, 2016
New Therapy Treats Autoimmune Disease Without Harming Normal Immunity
Preclinical study from Penn shows that engineered T cells can selectively target the antibody-producing cells that cause autoimmune disease.
Friday, July 01, 2016
New Antiviral Drugs Could Come from DNA "Scrunching"
University of Pennsylvania scientists show that DNA “scrunching” may be responsible for driving DNA into a virus during replication.
Friday, June 10, 2016
Better Animal Model to Improve HIV Vaccine Development
Penn study identifies a new tool to produce better HIV vaccine designs.
Tuesday, June 07, 2016
Testing Non-Breast/Ovarian Cancer Genes
Researchers have found that expanding gene panel beyond breast/ovarian cancer genes in these patients does not add any clinical benefit. Instead, testing has produced more questions than answers.
Saturday, May 21, 2016
How Did The Giraffe Get Its Long Neck?
Clues about the evolution of the giraffe’s long neck have now been revealed by new genome sequencing.
Wednesday, May 18, 2016
New Pathway That May Trigger Asthma Discovered
Finding could lead to better drugs for the many asthma patients who don’t respond well to current medications.
Wednesday, April 20, 2016
Scientific News
How it Works: Advanced Data Analysis Using Visualization
Visualisation of data can be used to help molecular biologists tackle the vast datasets their experiments create.
Unravelling the Role of Key Genes and DNA Methylation in Blood Cell Malignancies
Researchers from the University of Nebraska Medical Center have demonstrated the role of Dnmt3a in safeguarding normal haematopoiesis.
Salford Lung Study - The First Real World Clinical Trial
In this podcast, we learn about the Salford Lung Study and its potential to revolutionize the way we assess new drugs and treatments around the world.
A Simple Tool for Clinical and Postmortem Toxicological Analysis
In this study, GC-MS is used for the determination of clozapine, and five antidepressants in human plasma, serum and whole blood.
Identification of Individual Red Blood Cells by Raman Microspectroscopy
In this study, Raman Microspectroscopy was used to identify individual red blood cells.
Fighting Cancer with the Power of Immunity
Researchers at MIT have used a combination of four different therapies to activate both of the immune system’s two branches, producing a coordinated attack that led to the complete disappearance of large, aggressive tumors in mice.
NIH Researchers Unveil New Wound-Healing Role for Protein-Folding Gene in Mice
The study found that topical treatment of an Hsp60-containing gel dramatically accelerates wound closure in a diabetic mouse model.
50-Year-Old Bacteria Could Be Alternative Treatment Option for Cancer
Researchers have developed a non-toxic strain of Salmonella to penetrate and target cancer cells.
Promising Blood Test Fails to Yield Clues About Best Strategies for Bladder Cancer Treatment
Penn Medicine research challenges previous findings on utility of neutrophil-to-lymphocyte ratio as a biomarker.
Robotic Cleaning Technique Could Automate Neuroscience Research
New robotic cleaning technique allows pipettes used in patch-clamping to be re-used up to 11 or more times.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,500+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
5,200+ scientific videos