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!
Zebrafish's near 360 degree UV-vision knocks stripes off Google Street View
22.06.2018 | University of Sussex
New cellular pathway helps explain how inflammation leads to artery disease
22.06.2018 | Cedars-Sinai Medical Center
In a recent publication in the renowned journal Optica, scientists of Leibniz-Institute of Photonic Technology (Leibniz IPHT) in Jena showed that they can accurately control the optical properties of liquid-core fiber lasers and therefore their spectral band width by temperature and pressure tuning.
Already last year, the researchers provided experimental proof of a new dynamic of hybrid solitons– temporally and spectrally stationary light waves resulting...
Scientists from the University of Freiburg and the University of Basel identified a master regulator for bone regeneration. Prasad Shastri, Professor of...
Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.
Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...
The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.
Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.
An international team of scientists has discovered a new way to transfer image information through multimodal fibers with almost no distortion - even if the fiber is bent. The results of the study, to which scientist from the Leibniz-Institute of Photonic Technology Jena (Leibniz IPHT) contributed, were published on 6thJune in the highly-cited journal Physical Review Letters.
Endoscopes allow doctors to see into a patient’s body like through a keyhole. Typically, the images are transmitted via a bundle of several hundreds of optical...
13.06.2018 | Event News
08.06.2018 | Event News
05.06.2018 | Event News
22.06.2018 | Materials Sciences
22.06.2018 | Earth Sciences
22.06.2018 | Life Sciences