These microbial partners provide beneficial aid in multiple ways – from helping digest food to the development of a healthy immune system.
This is an inflamed mouse lung. Infiltrating innate immune cells are stained in red and green. Credit: Meera Nair, PhD, Michael Abt, PhD, David Artis, PhD; Perelman School of Medicine, UPenn
In a new study published online in the journal Immunity, David Artis, PhD, associate professor of Microbiology, and Michael Abt, PhD, a postdoctoral researcher in the Artis lab, Perelman School of Medicine, University of Pennsylvania, show that commensal bacteria are also essential to fight off viral infections.
"From our studies in mice, we found that signals derived from these beneficial microbes are essential for optimal immune responses to experimental viral infections," says Artis. "In one way we could consider these microbes as our 'brothers in arms' in the fight against infectious diseases." Artis is also an associate professor of Pathobiology in the Penn School of Veterinary Medicine.
Signals from commensal bacteria influence immune-cell development and susceptibility to infectious or inflammatory diseases. Commensal microbial communities colonize barrier surfaces of the skin, vaginal, upper respiratory, and gastrointestinal tracts of mammals and consist of bacteria, fungi, protozoa, and viruses. The largest and most diverse microbial communities live in the intestine.
Previous studies in patients have associated alterations in bacterial communities with susceptibility to diabetes, obesity, cancer, inflammatory bowel disease, allergy, and other disorders. Despite knowing all of this, exactly how commensal bacteria regulate immunity after being exposed to pathogens is not well understood.
To get a better picture of how these live-in bacteria are beneficial, the Artis lab used several lines of investigation. First, they demonstrated that mice -- treated with antibiotics to reduce numbers of commensal bacteria -- exhibit an impaired antiviral immune response and a substantially delayed clearance of a systemic virus or influenza virus that infects the airways. What's more, the treated mice had severely damaged airways and increased rate of death after the experimental influenza virus infection, demonstrating that alterations in commensal bacterial communities can have a negative impact on immunity against viruses.
Next, they profiled the genes that were expressed in immune cells called macrophages isolated from the antibiotic-treated mice. These data revealed a decreased expression of genes associated with antiviral immunity. In addition, macrophages from antibiotic-treated mice showed defective responses to interferons, proteins made and released in response to viruses, bacteria, parasites, or tumor cells. Under normal circumstances, interferons facilitate communication between cells to trigger the immune cells that attack pathogens or tumors. The antibiotic-treated mice also had an impaired capacity to limit viral replication. However, when mice were treated with a compound that restored interferon responsiveness, protective antiviral immunity was re-established.
"It is remarkable that signals derived from one type of microbe, in this case bacteria, can have such a profound effect on immune responses to viruses that are a very different type of microbe," says first author Abt. "Just like we would set a thermostat to regulate when a heater should come on, our studies indicate that signals derived from commensal bacteria are required to set the activation threshold of the immune system."
Taken together, these lines of evidence indicate that signals from commensal bacteria beneficially stimulate immune cells in a way that is optimal for antiviral immunity. "Although more work needs to be done, these findings could illuminate new ways to promote better immunity to potentially life-threatening viral infections," adds Artis.
This research is supported by the National Institutes of Health National Institute of Allergy and Infectious Disease(grants AI061570, AI087990, AI074878, AI095608, AI091759, AI095466, AI071309, AI078897, AI095608, AI083022, AI077098, HHSN266200500030C, T32-AI05528, T32-AI007532, T32-RR007063, K08-DK093784, T32-AI007324); the Irvington Institute Postdoctoral Fellowship of the Cancer Research Institute; the Burroughs Wellcome Fund, the National Institute of Diabetes and Digestive and Kidney Disease Center for the Molecular Studies in Digestive and Liver Disease and the Molecular Pathology and Imaging Core.
In addition to Artis and Abt, co-authors are Lisa C. Osborne, Laurel A. Monticelli, Travis A. Doering, Theresa Alenghat, Gregory F. Sonnenberg, Michael A. Paley, Marcelo Antenus, Katie L. Williams, and E. John Wherry, all from Penn, and Jan Erikson from the Wistar Institute.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.
Karen Kreeger | EurekAlert!
Transforming plant cells from generalists to specialists
07.12.2016 | Duke University
What happens in the cell nucleus after fertilization
06.12.2016 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.
Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...
Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...
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,...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
07.12.2016 | Earth Sciences
07.12.2016 | Earth Sciences
07.12.2016 | Materials Sciences