The receptor called Dectin-1, studied in the laboratory of David Underhill, PhD, an associate professor in Cedars-Sinai’s Inflammatory Bowel and Immunobiology Research Institute, detects fungi and instructs white blood cells whether to expend the energy needed to devour the invading pathogens. The findings are featured as the cover story in the April 28 edition of Nature.
Although scientists long have theorized how immune cells recognize microbial debris sloughed from invading organisms at some distance from themselves, this study establishes a model to explain how immune cells determine when pathogens are directly in contact with their surface and thus pose a significantly greater risk, demanding rapid destruction.
The study is important because it moves scientists one step closer to understanding the mysteries of how our bodies mount an immune response to fight disease.
In early stages of infection, white blood cells patrol the body looking for invading pathogens. Dectin-1, a receptor on the surface of white blood cells, recognizes specific components of fungal cell walls, and alerts or “switches on” the immune cells to prepare to fight the infection.
“Our lab has been studying Dectin-1, which directs white blood cells to eat and kill the fungi that they encounter directly, but to ignore soluble material sloughed off of the fungal surface which does not pose an immediate threat,” said Helen Goodridge, PhD, first author on the study and a researcher in the laboratory headed by Underhill. “This is important because phagocytosis and anti-microbial defense responses are energy-intensive and destructive, and should only be used when absolutely necessary.”
During phagocytosis, a white blood cell encounters a microbe, engulfs it, and eats it. Once inside the cell, the microbe can be killed using a combination of degradative enzymes, highly reactive chemicals, and an acidic environment.
A molecular structure that the Underhill lab calls a “phagocytic synapse” forms at the surface of the white blood cell when Dectin-1 detects fungi. As a phagocytic synapse forms, two inhibitory proteins that block transmission of signals inside the white blood cell are pushed aside. This allows Dectin-1 to instruct the cell to respond. The phagocytic synapse does not form when Dectin-1 encounters soluble fungal debris, so the white blood cell does not respond.
“The phagocytic synapse resembles another molecular structure, the ‘immunological synapse.’ It is critical at later stages of an immune response,” said Underhill. “It appears that the phagocytic synapse may be an evolutionary precursor of the immunological synapse.”
The study was funded by the National Institutes of Health, the American Heart Association, and the Crohn’s and Colitis Foundation of America. Underhill, who also directs the PhD Program in Biomedical Sciences and Translational Medicine at Cedars-Sinai, is the Medical Center’s Janis and William Wetsman Family Chair in Inflammatory Bowel Disease Research.
Nationally known for its high quality patient care, the Cedars-Sinai Health System includes a major research enterprise and ranks among the top 10 independent medical centers in terms of NIH research funding. With more than 850 research projects under way, Cedars-Sinai focuses on translational studies that move advances directly from the laboratory to the bedside.
Nicole White | Cedars-Sinai Medical Center
MicroRNA helps cancer evade immune system
19.09.2017 | Salk Institute
Ruby: Jacobs University scientists are collaborating in the development of a new type of chocolate
18.09.2017 | Jacobs University Bremen gGmbH
Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!
When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...
For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.
Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...
MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems Holding GmbH about commercial use of a multi-well tissue plate for automated and reliable tissue engineering & drug testing.
MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems...
Pathogenic bacteria are becoming resistant to common antibiotics to an ever increasing degree. One of the most difficult germs is Pseudomonas aeruginosa, a...
Scientists from the MPI for Chemical Energy Conversion report in the first issue of the new journal JOULE.
Cell Press has just released the first issue of Joule, a new journal dedicated to sustainable energy research. In this issue James Birrell, Olaf Rüdiger,...
19.09.2017 | Event News
12.09.2017 | Event News
06.09.2017 | Event News
19.09.2017 | Event News
19.09.2017 | Physics and Astronomy
19.09.2017 | Power and Electrical Engineering