In recent years, much research has focused on understanding precisely what the bacterium S aureus does within the host to disrupt the immune system. Despite considerable advances, however, it remained unclear how the host’s immune system responded to the infection and why some people are apt to get more severe staphylococcal infections than others.
By using gene expression profiling, a process that summarizes how individual genes are being activated or suppressed in response to the infection, UT Southwestern researchers pinpointed how an individual’s immune system responds to a S aureus infection at the genetic level.
“The beauty of our study is that we were able to use existing technology to understand in a real clinical setting what’s going on in actual humans – not models, not cells, not mice, but humans,” said Dr. Monica Ardura, instructor of pediatrics at UT Southwestern and lead author of the study available online in PLoS One, the Public Library of Science’s online journal. “We have provided the first description of a pattern of response within an individual’s immune system that is very consistent, very reproducible and very intense.”
The immune system consists of two components: the innate system, which provides immediate defense against infection; and the adaptive system, whose memory cells are called into action to fight off subsequent infections.
In this study, researchers extracted ribonucleic acid from a drop of blood and placed it on a special gene chip called a microarray, which probes the entire human genome to determine which genes are turned on or off. They found that in children with invasive staphylococcal infections, the genes involved in the body’s innate immune response are overactivated while those associated with the adaptive immune system are suppressed.
“It’s a very sophisticated and complex dysregulation of the immune system, but our findings prove that there’s consistency in the immune response to the staphylococcus bacterium,” Dr. Ardura said. “Now that we know how the immune system responds, the question is whether we can use this to predict patient outcomes or differentiate the sickest patients from the less sick ones. How can we use this knowledge to develop better therapies?”
Researchers used blood samples collected between 2001 and 2005 from 77 children – 53 hospitalized at Children’s Medical Center Dallas with invasive S aureus infections and 24 controls. The control samples were collected from healthy children attending either well-child clinic or undergoing elective surgical procedures. Children with underlying chronic diseases, immunodeficiency, multiple infections, and those who received steroids or other immunomodulatory therapies were excluded from the study.
The children ranged in age from a few months to 15 years and included 43 boys and 34 girls. Those with S aureus infections – both methicillin-resistant (MRSA) and methicillin-susceptible (MSSA) – were matched with healthy controls for age, sex and race. The researchers also characterized the extent as well as the type of infection in each patient to make sure that the strain of bacteria didn’t influence the results.
Dr. Ardura stressed that more research is needed because the results represent a one-time snapshot of what’s going on in the cell during an invasive staphylococcal infection.
“The median time to get the blood sample was day four because we wanted to make sure the hospitalized children had a S aureus infection, and its takes four days to have final identification of the bacterial pathogen,” she said.
The next step, Dr. Ardura said, is to study those dynamics in patients before, during and after infection. They also hope to understand better how various staph-infection therapies affect treatment.
“This is a very important proof-of-concept that the information is there for us to grab,” Dr. Ardura said. “Now we have to begin to understand what that data tells us.”
Other UT Southwestern researchers involved in the study were Romain Banchereau, student research assistant in pediatrics; Dr. Asuncion Mejias, assistant professor of pediatrics; and Dr. Octavio Ramilo, former professor of pediatrics and senior author of the study. Dr. Ramilo recently moved to Nationwide Children’s Hospital in Columbus, Ohio. Researchers from the Baylor Institute for Immunology Research, Baylor National Institute of Allergy and Infectious Diseases Cooperative Center for Translational Research on Human Immunology and Biodefense, the Baylor Institute for Immunology Research and the Baylor Research Institute also contributed.
The work was supported by the National Institutes of Health, the Center for Lupus Research and the Baylor Health Care System Foundation.
Visit www.utsouthwestern.org/pediatrics to learn more about pediatric clinical services at UT Southwestern.
Dr. Monica Ardura -- http://www.utsouthwestern.edu/findfac/professional/0,2356,68518,00.html
Dr. Octavio Ramilo -- http://www.utsouthwestern.edu/findfac/professional/0,2356,15916,00.html
Kristen Holland Shear | Newswise Science News
A Map of the Cell’s Power Station
18.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau
On the way to developing a new active ingredient against chronic infections
18.08.2017 | Deutsches Zentrum für Infektionsforschung
Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.
As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...
Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.
Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...
For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.
While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...
An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.
The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...
A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.
Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...
16.08.2017 | Event News
04.08.2017 | Event News
26.07.2017 | Event News
18.08.2017 | Life Sciences
18.08.2017 | Physics and Astronomy
18.08.2017 | Materials Sciences