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
Water forms 'spine of hydration' around DNA, group finds
26.05.2017 | Cornell University
How herpesviruses win the footrace against the immune system
26.05.2017 | Helmholtz-Zentrum für Infektionsforschung
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....
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....
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...
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...
An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...
24.05.2017 | Event News
23.05.2017 | Event News
22.05.2017 | Event News
26.05.2017 | Life Sciences
26.05.2017 | Life Sciences
26.05.2017 | Physics and Astronomy