Scientists at the Institute of Molecular Biotechnology (IMBA) and the Max F. Perutz Laboratories (MFPL) in Vienna have discovered a new way to turn the immune system’s weapons against fungal invaders. This knowledge could lead to the development of new and improved anti-fungal treatments.
For most people, a simple case of thrush or athlete’s foot can be quickly and easily treated using over-the-counter anti-fungal creams and pills. However, even with medication, fungal pathogens can overwhelm a weakened immune system and cause systemic infections – as in people with HIV/AIDS, or organ transplant recipients, for example – posing a severe health risk.
In fact, fungal pathogens have been classified as “hidden killers” and an estimated 1.5 million people around the world die from such systemic infections every year. There is yet no effective medicine available for systemic fungal infections.
Knowing the enemy
When fungal cells enter the body, they stand out from our own cells because they are ‘flagged’ with unique patterns of molecular markers. These ‘pathogen-associated molecular patterns’, or PAMPs for short, are recognised by receptor proteins on cells of the immune system. These receptors then activate signalling molecules triggering a cascade of different immune functions, such as inflammation, aimed at recruiting immune cells to the infected area. Those recruited immune cells will then, for example via the production of highly toxic reactive oxygen species, eliminate fungal pathogens.
“Unleashing” an immune response
Candida albicans is recognized by certain PAMP receptors, called Dectins, and triggers activation of the signalling molecule SYK. The first authors of the study, Gerald Wirnsberger (IMBA) and Florian Zwolanek (MFPL), now discovered that the protein CBL-B acts as a ‘brake’ in this pathway: when CBL-B is present, Dectin and SYK activity are dampened and immune responses are eventually ‘switched off’, but when CBL-B is absent, Dectin/SYK get over-activated and a protective anti-fungal immune responses occur.
Using this knowledge, the two research groups around Josef Penninger (IMBA) and Karl Kuchler (MFPL) – designed an inhibitory peptide to block CBL-B activity and thereby unleash defence mechanisms against invading fungal pathogens. After successfully testing this peptide with lab-grown cells, the peptide was used to treat Candida albicans infected mice. While untreated mice succumbed to the lethal infection, peptide treatment provided complete protection from fungal disease.
Gerald Wirnsberger explains: “This work constitutes a novel paradigm in antifungal therapy – a pharmacological modulation of the host immune response mediated by CBLB. A fundamental understanding of how molecular mechanisms either boost or damp our immune response against Candida albicans will pave the way for a drugs against deadly fungal infections”.
„Inhibition of CBLB protects from lethal Candida albicans sepsis“.
Gerald Wirnsberger, Florian Zwolanek, Tomoko Asaoka, Ivona Kozieradzki, Luigi Tortola, Reiner A Wimmer, Anoop Kavirayani, Friedrich Fresser, Gottfried Baier, Wallace Y Langdon, Fumiyo Ikeda, Karl Kuchler & Josef M Penninger.
Nature Medicine, July 18, 2016. doi: 10.1038/nm.4134.
Dr. Bohrgasse 3, 1030 Vienna, Austria
Tel.: +43 664 808 47 3628
Mag. Ines Méhu-Blantar | idw - Informationsdienst Wissenschaft
Single-stranded DNA and RNA origami go live
15.12.2017 | Wyss Institute for Biologically Inspired Engineering at Harvard
New antbird species discovered in Peru by LSU ornithologists
15.12.2017 | Louisiana State University
DNA molecules that follow specific instructions could offer more precise molecular control of synthetic chemical systems, a discovery that opens the door for engineers to create molecular machines with new and complex behaviors.
Researchers have created chemical amplifiers and a chemical oscillator using a systematic method that has the potential to embed sophisticated circuit...
MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.
Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...
Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...
Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.
To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...
The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.
Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...
11.12.2017 | Event News
08.12.2017 | Event News
07.12.2017 | Event News
15.12.2017 | Power and Electrical Engineering
15.12.2017 | Materials Sciences
15.12.2017 | Life Sciences