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.
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 | Source: Newswise
Further information: www.unc.edu
More articles from Life Sciences:
ASU researchers discover chameleons use colorful language to communicate
12.12.2013 | Arizona State University
Sleep-deprived mice show connections among lack of shut-eye, diabetes, age
12.12.2013 | University of Pennsylvania School of Medicine
A unique solar panel design made with a new ceramic material points the way to potentially providing sustainable power cheaper, more efficiently, and requiring less manufacturing time.
It also reaches a four-decade-old goal of discovering a bulk photovoltaic material that can harness energy from visible and infrared light, not just ultraviolet light.
Scaling up this new design from its tablet-size prototype to a full-size solar panel would be a large step toward making solar power affordable compared with ...
Atlantische Flohkrebse pflanzen sich jetzt auch in arktischen Gewässern fort
Biologen des Alfred-Wegener-Institutes, Helmholtz-Zentrum für Polar- und Meeresforschung (AWI), haben zum ersten Mal nachgewiesen, dass sich in den arktischen Gewässern westlich Spitzbergens auch Flohkrebse aus dem wärmeren Atlantik fortpflanzen.
Diese überraschende Entdeckung deute auf einen möglichen Wandel der arktischen Zooplankton-Gemeinschaft hin, berichten die Wissenschaftler und Wissenschaftlerinnen in der Fachzeitschrift Marine Ecology ...
The molecular architecture of three key proteins and their complexes reveals how plants fine-tune their immune response to pathogens
Plants rarely get sick in their natural environment. When the threat of infection arises, a quick decision is made about the necessary countermeasures. The course is set by a protein which forms complexes with its partner proteins for this purpose.
Jane Parker from the Max Planck Institute for Plant Breeding ...
Researchers studying speciation of butterfly orchids on the Azores have been startled to discover that the answer to a long-debated question "Do the islands support one species or two species?" is actually "three species".
Hochstetter's Butterfly-orchid, newly recognized following application of a battery of scientific techniques and reveling in a complex taxonomic history worthy of Sherlock Holmes, is arguably Europe's rarest orchid species. Under threat in its mountain-top retreat, the orchid urgently requires conservation recognition.
A lavishly illustrated publication, titled "Systematic revision of Platanthera in ...
Researchers from Brown University and the University of Hawaii have found some mineralogical surprises in the Moon's largest impact crater.
Data from the Moon Mineralogy Mapper that flew aboard India's Chandrayaan-1 lunar orbiter shows a diverse mineralogy in the subsurface of the giant South Pole Aitken basin.
The differing mineral signatures could be reflective of the minerals dredged up at the time of the giant impact 4 billion years ago, ...
12.12.2013 | Life Sciences
12.12.2013 | Earth Sciences
12.12.2013 | Studies and Analyses
11.12.2013 | Event News
10.12.2013 | Event News
05.12.2013 | Event News