Immune cells that are the body’s front-line defense don’t necessarily rest quietly until invading bacteria lock onto receptors on their outside skins and rouse them to action, as previously thought. In a new paper, University of Michigan scientists describe their findings that bacteria can barge inside these guard cells and independently initiate a powerful immune response.
The study, published online ahead of print in the April issue of the journal Immunity and accompanied by a special commentary, adds important new details to an emerging picture of how the body recognizes invading bacteria and responds. The work of the U-M team and researchers elsewhere — now taking place in laboratory animal studies — offers a different way of thinking about how best to design future human vaccines, as well as drugs that could more precisely target the body’s inflammatory response in rheumatoid arthritis and some other autoimmune diseases.
“In our study, the presence of bacterial microbes inside the cell is what triggers the immune response. That creates a new perspective for developing new drugs,” says senior author Gabriel Nunez, M.D., the Paul H. de Kruif professor of pathology at the U-M Medical School and a member of the U-M Comprehensive Cancer Center.
For years, scientists have believed that when bacteria invade the body, they set off alarms in the immune system by interacting with receptors on a cell’s surface. But, now new studies are revealing that bacteria can also plunge inside immune system cells and trigger the immune response there. In the new study, Nunez’ team sheds light on one major pathway in which this process occurs.
When invading bacteria enter immune system cells, a protein called cryopyrin, present in the fluid inside the cells, responds and activates a key pathogen-fighting molecule, Nunez’ team reported last year in Nature. Cryopyrin is implicated in the development of several inflammatory syndromes characterized by recurrent fever, skin rash and arthritis.
Cryopyrin triggers a key enzyme involved in the body’s inflammatory response, capsase-1, which in turn causes production of IL-1beta, a powerful molecule which signals the immune system to attack pathogens and induces fever to help the body fend off infection. IL-1beta plays an important role, too, in excessive immune system activity in inflammatory diseases.
The researchers report in the new paper how cryopyrin is activated to start the process. In experiments that exposed mouse immune cells called macrophages to bacteria, Thirumala-Devi Kanneganti, Ph.D., a U-M research investigator in pathology, and Mohamed Lamkanfi, Ph. D, a U-M research fellow, the study’s co-first authors, find that cryopyrin’s call to action inside the cells occurs without requiring a well-known set of cell-surface receptors called Toll-like receptors or TLRs. ”We prove that these TLRs are not required to activate cryopyrin. That is a major step,” says Nunez.
Instead, bacteria were able to enter the cells through a pore in the cell membrane, and stimulate the cryopyrin-initiated immune response without activating TLRs. The researchers discovered that a protein called pannexin-1 creates the pore, like a devious undersea diver drilling a hole in a ship hull.
The team’s work joins a growing body of research revealing the importance of recently discovered receptors such as cryopyrin inside cells, known collectively as NOD-like receptors. Knowledge about NOD-like receptors is moving forward rapidly and will contribute to a fuller understanding of the human immune system, say the U-M researchers.
Anne Rueter | EurekAlert!
Symbiotic bacteria: from hitchhiker to beetle bodyguard
28.04.2017 | Johannes Gutenberg-Universität Mainz
Nose2Brain – Better Therapy for Multiple Sclerosis
28.04.2017 | Fraunhofer-Institut für Grenzflächen- und Bioverfahrenstechnik IGB
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
28.04.2017 | Event News
20.04.2017 | Event News
18.04.2017 | Event News
28.04.2017 | Medical Engineering
28.04.2017 | Earth Sciences
28.04.2017 | Life Sciences