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

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 3,200+ scientific posters on ePosters
  • More Than 4,600+ 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 TechnologyNetworks.com 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 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
Parkinson's "Good" Genotype Makes Less of "Bad" Protein
Penn study uncovers genetic variation that predicted type and rate of physical decline in patients with Parkinson's disease.
Friday, April 15, 2016
Revealing the Function of Mysterious RNAs
Study co-led by Penn Medicine researcher shows non-coding DNA acting as enhancer of nearby gene's expression.
Tuesday, April 12, 2016
Seeing Cell to Cell Differences
Seeing differences between individual cells for first time explains symptoms of rare genetic disorders, finds penn study.
Tuesday, April 05, 2016
Countless New, Cleaner Uses of Methane
Chemists have demonstrated the potential to use methane as a versatile chemical building block with which to make more complex molecules.
Tuesday, March 29, 2016
Mechanism Explains Female Bias in Autoimmunity

Tuesday, March 22, 2016
Model Sheds Light on Human Genome Variability
Fresh approach identifies genetic risk factors that influence complex human diseases
Tuesday, February 23, 2016
Machine Learning Uncovers Unknown Bacterial Features
Technique robustly identified characteristic gene expression patterns in response to antibiotics, low oxygen conditions.
Monday, January 25, 2016
Genetic Cause of Heart Disease
Penn study sheds light on a genetic cause of heart disease.
Wednesday, December 16, 2015
Gene Pair Plays Crucial Role in Colon Cancer
In a new study researchers from the University of Pennsylvania describe two related genes in the Musashi family that are required for colon cancer to develop, and that may be useful targets for effective treatment.
Monday, December 07, 2015
Penn Engineering Team Showcases ‘Eye-on-a-Chip’ Technology
These small plastic chips contain microfluidic channels, carefully designed so that human cells can grow in them in a way that simulates the three-dimensional environments they would normally inhabit in the body.
Thursday, November 19, 2015
Scientific News
Platelets are the Pathfinders for Leukocyte Extravasation During Inflammation
Findings from the study could help in the prevention and treatment of inflammatory pathologies.
ASMS 2016: Targeting Mass Spectrometry Tools for the Masses
The expanding application range of MS in life sciences, food, energy, and health sciences research was highlighted at this year's ASMS meeting in San Antonio, Texas.
Benchtop Automation Trends
Gain a better understanding of current interest in and future deployment of benchtop automated systems.
Manufactured Stem Cells to Advance Clinical Research
Clinical-grade cell line will enable development of new therapies and accelerate early-stage clinical research.
Dengue Virus Exposure May Amplify Zika Infection
Researchers at Imperial College London have found that the previous exposure to the dengue virus may increase the potency of Zika infection.
Gender Determination in Forensic Investigations
This study investigated the effectiveness of lip print analysis as a tool in gender determination.
Identifying Novel Types of Forensic Markers in Degraded DNA
Scientists have tried to verify the nucleosome protection hypothesis by discovering STRs within nucleosome core regions, using whole genome sequencing.
Proteins in Blood of Heart Disease Patients May Predict Adverse Events
Nine-protein test shown superior to conventional assessments of risk.
Higher Frequency of Huntington's Disease Mutations Discovered
University of Aberdeen study shows that the gene change that causes Huntington's disease is much more common than previously thought.
Starving Stem Cells May Enable Scientists To Build Better Blood Vessels
Researchers from the University of Illinois at Chicago College of Medicine have uncovered how changes in metabolism of human embryonic stem cells help coax them to mature into specific cell types — and may improve their function in engineered organs or tissues.
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
3,200+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,600+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!