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!
Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute
Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water
In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...
The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.
Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
02.12.2016 | Medical Engineering
02.12.2016 | Agricultural and Forestry Science
02.12.2016 | Physics and Astronomy