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
27.03.2015 | Oak Ridge National Laboratory
How did the chicken cross the sea?
27.03.2015 | Michigan State University
In an experiment at the Department of Energy's SLAC National Accelerator Laboratory, scientists precisely measured the temperature and structure of aluminum as...
The IPH presents a solution at HANNOVER MESSE 2015 to make ship traffic more reliable while decreasing the maintenance costs at the same time. In cooperation with project partners, the research institute from Hannover, Germany, has developed a sensor system which continuously monitors the condition of the marine gearbox, thus preventing breakdowns. Special feature: the monitoring system works wirelessly and energy-autonomously. The required electrical power is generated where it is needed – directly at the sensor.
As well as cars need to be certified regularly (in Germany by the TÜV – Technical Inspection Association), ships need to be inspected – if the powertrain stops...
When an earthquake hits, the faster first responders can get to an impacted area, the more likely infrastructure--and lives--can be saved.
The Atlantic overturning is one of Earth’s most important heat transport systems, pumping warm water northwards and cold water southwards. Also known as the Gulf Stream system, it is responsible for the mild climate in northwestern Europe.
Scientists now found evidence for a slowdown of the overturning – multiple lines of observation suggest that in recent decades, the current system has been...
Because they are regularly subjected to heavy vehicle traffic, emissions, moisture and salt, above- and underground parking garages, as well as bridges, frequently experience large areas of corrosion. Most inspection systems to date have only been capable of inspecting smaller surface areas.
From April 13 to April 17 at the Hannover Messe (hall 2, exhibit booth C16), engineers from the Fraunhofer Institute for Nondestructive Testing IZFP will be...
25.03.2015 | Event News
19.03.2015 | Event News
17.03.2015 | Event News
27.03.2015 | Agricultural and Forestry Science
27.03.2015 | Materials Sciences
27.03.2015 | Ecology, The Environment and Conservation