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 Meadows beat out shrubs when it comes to storing carbon
23.11.2017 | Norwegian University of Science and Technology

nachricht Migrating Cells: Folds in the cell membrane supply material for necessary blebs
23.11.2017 | Westfälische Wilhelms-Universität Münster

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Frictional Heat Powers Hydrothermal Activity on Enceladus

Computer simulation shows how the icy moon heats water in a porous rock core

Heat from the friction of rocks caused by tidal forces could be the “engine” for the hydrothermal activity on Saturn's moon Enceladus. This presupposes that...

Im Focus: Nanoparticles help with malaria diagnosis – new rapid test in development

The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.

Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

Underwater acoustic localization of marine mammals and vehicles

23.11.2017 | Information Technology

Enhancing the quantum sensing capabilities of diamond

23.11.2017 | Physics and Astronomy

Meadows beat out shrubs when it comes to storing carbon

23.11.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>