Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Immune Cell Suicide Alarm Helps Destroy Escaping Bacteria

25.01.2013
Cells in the immune system called macrophages normally engulf and kill intruding bacteria, holding them inside a membrane-bound bag called a vacuole, where they kill and digest them.

Some bacteria thwart this effort by ripping the bag open and then escaping into the macrophage’s nutrient-rich cytosol compartment, where they divide and could eventually go on to invade other cells.


Miao lab, UNC School of Medicine.

Shown in red are bacteria that have invaded host cells and escaped into the interior cytosolic compartment of the cell.

But research from the University of North Carolina School of Medicine shows that macrophages have a suicide alarm system, a signaling pathway to detect this escape into the cytosol. The pathway activates an enzyme, called caspase-11, that triggers a program in the macrophage to destroy itself.

“It’s almost like a thief sneaking into the house not knowing an alarm will go off to knock down the walls and expose him to capture by the police,” says study senior and corresponding author Edward Miao, PhD, assistant professor of microbiology and immunology at UNC. “In the macrophage, this cell death, called pyroptosis, expels the bacterium from the cell, exposing it to other immune defense mechanisms.”

A report of the research appears online in the journal Science on Thursday January 24, 2013.

Miao, also a member of the UNC Lineberger Comprehensive Cancer Center, says the new findings show that having this detection pathway protects mice from lethal infection with the type of vacuole-escaping Burkholderia species: B. thailandensis and B. pseudomallei.

Both are close relatives. But they differ in lethality. B. pseudomallei is potentially a biological weapon. Used in a spray, it could potentially infect people via aerosol route, causing sickness and death. Moreover, it also could fall into a latent phase, “essentially turning into a ‘sleeper’ inside the lungs and hiding there for decades,” Miao explains. In contrast, B. thailandensis, which shares many properties with its species counterpart, is not normally able to cause any disease or infection

These environmental bacteria are ubiquitous throughout S.E. Asia, and were it not for the caspase-11 pathway defense system, that part of the world could be uninhabitable, Miao points out.

This grim possibility clearly emerged in the study. Mice that lack the caspase-11 detection pathway succumb to infection not only by B. pseudomallei, but also to the normally benign B. thailandensis. “Thus caspase-11 is critical for surviving exposure to ubiquitous environmental pathogens,” the authors conclude.

Miao points to research elsewhere showing that the pathway’s abnormal activation in people with septic shock, overwhelming bacterial infection of the blood, is associated with death. “We discovered what the pathway is supposed to do, which may help find ways to tone it down in people with that critical condition.

As to bioterrorism, the researcher says it may be possible to use certain drugs already on the market that safely induce the caspase-11 pathway. “Since this pathway requires pre-stimulation with interferon cytokines, it is conceivable that pre-treating people with interferon drugs could ameliorate a bioterror incident. This could be quite important in the case of Burkholderia, since these bacteria are naturally resistant to numerous antibiotics.

“But first we have to find out if they would work in animal models, and consider the logistics of interferon stockpiling, which are currently cost prohibitive.”

UNC co-authors are Youssef Aachoui, Jon A. Hagar, Peggy A. Cotter and Christine G. Campos. Alan Aderem, Irina A. Leaf, Daniel E. Zak are from Seattle Biomedical Research Institute, Seattle, Wash. Russell E. Vance, Mary F. Fontana and Michael Tan are from the department of molecular and cell biology, University of California at Berkeley.

This work was supported by NIH grants AI097518 (E.A.M.) and AI057141 (E.A.M. and A.A.), AI065359 (P.A.C.), AI075039 (R.E.V.), AI080749 (R.E.V.), and AI063302 (R.E.V.) Investigator Awards from the Burroughs Wellcome Fund and Cancer Research Institute (R.E.V.), and an NSF graduate fellowship (M.F.F.).

Les Lang | Newswise
Further information:
http://www.unc.edu

More articles from Life Sciences:

nachricht Toward a 'smart' patch that automatically delivers insulin when needed
18.01.2017 | American Chemical Society

nachricht 127 at one blow...
18.01.2017 | Stiftung Zoologisches Forschungsmuseum Alexander Koenig, Leibniz-Institut für Biodiversität der Tiere

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

A big nano boost for solar cells

18.01.2017 | Power and Electrical Engineering

Glass's off-kilter harmonies

18.01.2017 | Materials Sciences

Toward a 'smart' patch that automatically delivers insulin when needed

18.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>