Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Inner weapons against allergies: Gut bacteria control allergic diseases

26.03.2012
When poet Walt Whitman wrote that we "contain multitudes," he was speaking metaphorically, but he was correct in the literal sense. Every human being carries over 100 trillion individual bacterial cells within the intestine -- ten times more cells than comprise the body itself.

Now, David Artis, PhD, associate professor of Microbiology, along with postdoctoral fellow David Hill, PhD, from the Perelman School of Medicine at the University of Pennsylvania, and collaborators from The Children's Hospital of Philadelphia and institutions in Japan and Germany, have found that these commensal bacteria might play an important role in influencing and controlling allergic inflammation. The commensal relationship that develops between humans and internal bacteria is one in which both humans and bacteria derive benefits.


This is a mouse lung stained to visualize differentiated epithelial cells and macrophages, a type of immune cell. Credit: David Hill, Ph.D., Perelman School of Medicine, University of Pennsylvania

The study -- appearing this week in Nature Medicine -- suggests that therapeutic targeting of immune cell responses to resident gut bacteria may be beneficial in treating allergic diseases.

The researchers build on previous work demonstrating that selective manipulation of the commensal bacterial population could affect the immune system. "Studies in human patients suggest that changes in commensal populations or exposure to broad spectrum antibiotics can predispose patients to the development of systemic allergic diseases," Hill explains. "In addition, previous studies in animal models have shown that commensal bacteria can influence local immune cells in the intestine. However, the cellular and molecular mechanisms by which commensal bacteria influence the host immune system, in particular the branches of the host immune system that regulate allergic inflammation, are not well understood."

Artis and his colleagues focused on the role of basophils, a type of white blood cell, in causing allergic inflammation, and the relationship between basophil responses and allergic disease.

The investigators administered broad-spectrum oral antibiotics to deplete certain types of bacteria in mice and to subsequently examine the affects on levels of circulating basophils in the blood. Using an animal-based model of allergic inflammation in the lung that shares characteristics with asthma in humans, they found that antibiotic treatment resulted in significantly elevated basophil responses and a marked increase in the amount of basophil-mediated allergic airway inflammation. Elevated serum levels of IgE, an important mediator in allergic disease, were also observed.

After the antibiotic-treated mice were exposed to house dust mite allergen (HDM), a human allergen and a model of allergic airway disease in mice, they showed higher basophil responses in the blood and lymph nodes as well as a heightened allergic response with increased inflammation in the lungs.

Germ-free mice, which are reared in a sterile environment and thus lack all live commensal bacteria, also showed similar responses to those observed in antibiotic-treated mice when exposed to HDM. This finding indicates that commensal bacteria-derived signals are responsible for maintaining normal basophil numbers in the steady-state.

Artis and his colleagues also found that serum concentrations of IgE and circulating basophil numbers were limited by B cell-intrinsic expression of myeloid differentiation factor 88 (MyD88), a protein known to play a role in the recognition of bacteria-derived factors. Signals derived from the commensal bacteria were found to act via IgE to control the number of circulating basophils by limiting the proliferation of basophil precursor cells in the bone marrow.

All of these findings indicate important new processes by which resident commensal bacterial populations influence and control basophil responses and thus influence the response to allergens in our environment.

"The identification of a mechanistic connection between commensal bacteria, basophils, and allergic disease illuminates several new avenues that could be targeted by future therapeutics to block or inhibit the development of allergic disease," Artis notes. Further study and identification of these commensal pathways could also have implications for other chronic diseases related to immune system functioning.

Artis and his colleagues hope to further understand this intricate interplay between the immune system and commensal bacteria. "It may be beneficial to identify the specific commensals and commensal-derived signals that regulate circulating basophil populations as this could lead to the development of new probiotic or other commensal-derived therapies," he says. The work makes clear that the bacterial multitudes within our bodies may have a function and a value never before appreciated.

This work was funded by grants from the National Institute of Allergy and Infectious Disease, the National Cancer Institute, the Burroughs Wellcome Fund, the Penn Genome Frontiers Institute, and the Penn Center for the Molecular Studies in Digestive and Liver Diseases.

Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $4.3 billion enterprise.

The Perelman School of Medicine is currently ranked #2 in U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $479.3 million awarded in the 2011 fiscal year.

The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania -- recognized as one of the nation's top 10 hospitals by U.S. News & World Report; Penn Presbyterian Medical Center; and Pennsylvania Hospital — the nation's first hospital, founded in 1751. Penn Medicine also includes additional patient care facilities and services throughout the Philadelphia region.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2011, Penn Medicine provided $854 million to benefit our community.

Karen Kreeger | EurekAlert!
Further information:
http://www.uphs.upenn.edu

More articles from Life Sciences:

nachricht MACC1 Gene Is an Independent Prognostic Biomarker for Survival in Klatskin Tumor Patients
31.08.2015 | Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtz-Gemeinschaft

nachricht Fish Oil-Diet Benefits May be Mediated by Gut Microbes
28.08.2015 | University of Gothenburg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: An engineered surface unsticks sticky water droplets

The leaves of the lotus flower, and other natural surfaces that repel water and dirt, have been the model for many types of engineered liquid-repelling surfaces. As slippery as these surfaces are, however, tiny water droplets still stick to them. Now, Penn State researchers have developed nano/micro-textured, highly slippery surfaces able to outperform these naturally inspired coatings, particularly when the water is a vapor or tiny droplets.

Enhancing the mobility of liquid droplets on rough surfaces could improve condensation heat transfer for power-plant heat exchangers, create more efficient...

Im Focus: Increasingly severe disturbances weaken world's temperate forests

Longer, more severe, and hotter droughts and a myriad of other threats, including diseases and more extensive and severe wildfires, are threatening to transform some of the world's temperate forests, a new study published in Science has found. Without informed management, some forests could convert to shrublands or grasslands within the coming decades.

"While we have been trying to manage for resilience of 20th century conditions, we realize now that we must prepare for transformations and attempt to ease...

Im Focus: OU astrophysicist and collaborators find supermassive black holes in quasar nearest Earth

A University of Oklahoma astrophysicist and his Chinese collaborator have found two supermassive black holes in Markarian 231, the nearest quasar to Earth, using observations from NASA's Hubble Space Telescope.

The discovery of two supermassive black holes--one larger one and a second, smaller one--are evidence of a binary black hole and suggests that supermassive...

Im Focus: What would a tsunami in the Mediterranean look like?

A team of European researchers have developed a model to simulate the impact of tsunamis generated by earthquakes and applied it to the Eastern Mediterranean. The results show how tsunami waves could hit and inundate coastal areas in southern Italy and Greece. The study is published today (27 August) in Ocean Science, an open access journal of the European Geosciences Union (EGU).

Though not as frequent as in the Pacific and Indian oceans, tsunamis also occur in the Mediterranean, mainly due to earthquakes generated when the African...

Im Focus: Self-healing landscape: landslides after earthquake

In mountainous regions earthquakes often cause strong landslides, which can be exacerbated by heavy rain. However, after an initial increase, the frequency of these mass wasting events, often enormous and dangerous, declines, in fact independently of meteorological events and aftershocks.

These new findings are presented by a German-Franco-Japanese team of geoscientists in the current issue of the journal Geology, under the lead of the GFZ...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Networking conference in Heidelberg for outstanding mathematicians and computer scientists

20.08.2015 | Event News

Scientists meet in Münster for the world’s largest Chitin und Chitosan Conference

20.08.2015 | Event News

Large agribusiness management strategies

19.08.2015 | Event News

 
Latest News

Siemens sells 18 industrial gas turbines to Thailand

01.09.2015 | Press release

An engineered surface unsticks sticky water droplets

01.09.2015 | Materials Sciences

New material science research may advance tech tools

01.09.2015 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>