Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Holding back immunity

06.02.2012
A ‘gatekeeper’ protein plays a critical role in helping immune cells to sound a warning after encountering signs of tumor growth or infection

When the body’s own cells turn into ticking time bombs, as in cases of viral infection or cancerous transformation, a mechanism known as ‘cross-presentation’ enables the immune system’s dendritic cells (DCs) to sound the alarm.


Figure 1: Compared to untreated dendritic cells (top), cells treated with an HSP90 inhibitor (radicicol) (bottom) tend to retain a larger percentage of the antigen ovalbumin (red; left) within membrane bound endosomes (green; middle). Endosomes are labeled with a stain that marks the membrane protein PKH67. Copyright : 2012 the National Academy of Sciences

“Dendritic cells first internalize cancerous or virus-infected cells through a mechanism called phagocytosis, and then process cellular antigens into short peptides,” explains Heiichiro Udono of the RIKEN Center for Allergy and Immunology in Yokohama. DCs subsequently present these fragments to killer T cells, which seek out and destroy other affected cells. Phagocytosed molecules travel within sealed membrane bubbles called endosomes, and new work from Udono and his colleagues has revealed insights into how these antigens are released into the cytosol prior to cross-presentation1.

Udono’s team focused on heat-shock protein 90 (HSP90), a molecule that previous studies have linked to cross-presentation. HSP90 comes in two forms, á and â, which perform overlapping roles. Mice need at least one of these proteins to live. Udono and colleagues succeeded in generating healthy mice that exclusively lack HSP90á. They found that, although HSP90â appears to make some contribution, the loss of HSP90á had a striking effect on antigen processing. DCs isolated from these mice showed defects in their capacity for cross-presentation, and failed to activate killer T cells efficiently following exposure to ovalbumin, a model antigen.

HSP90á-deficient DCs proved perfectly capable of internalizing ovalbumin within endosomes; however, they generally failed to release this antigen into the cytosol. The researchers noted a similar effect after treating genetically normal DCs with a chemical that inhibits HSP90á (Fig. 1), confirming the central role of this protein in endosomal release.

Udono and colleagues further demonstrated the extent of these defects by injecting HSP90á-deficient mice with cytochrome c, a protein that selectively eliminates a subpopulation of DCs after being taken up and released into the cytosol. Strikingly, cytochrome c treatment had a dramatically reduced effect on DCs from mutant mice relative to their wild-type counterparts. “This is the most sensitive in vivo assay to show antigen translocation to the cytosol,” says Udono. “This phenomenon was absent in HSP90á knockout mice, which makes me confident that our finding is important and has physiological relevance.”

Accordingly, Udono believes that molecules that modulate HSP90 activity might help clinicians to boost a patient’s immune counterattack against infection or cancer. “If we can control the expression levels of HSP90 and other heat shock proteins,” he says, “it could be of great benefit to human health.”

The corresponding author for this highlight is based at the Laboratory for Immunochaperones, RIKEN Research Center for Allergy and Immunology

gro-pr | Research asia research news
Further information:
http://www.riken.jp
http://www.researchsea.com

More articles from Life Sciences:

nachricht Water forms 'spine of hydration' around DNA, group finds
26.05.2017 | Cornell University

nachricht How herpesviruses win the footrace against the immune system
26.05.2017 | Helmholtz-Zentrum für Infektionsforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Can the immune system be boosted against Staphylococcus aureus by delivery of messenger RNA?

Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.

Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....

Im Focus: A quantum walk of photons

Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.

The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

Im Focus: World's thinnest hologram paves path to new 3-D world

Nano-hologram paves way for integration of 3-D holography into everyday electronics

An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

 
Latest News

How herpesviruses win the footrace against the immune system

26.05.2017 | Life Sciences

Water forms 'spine of hydration' around DNA, group finds

26.05.2017 | Life Sciences

First Juno science results supported by University of Leicester's Jupiter 'forecast'

26.05.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>