Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Targeting innate immunity in malaria

05.08.2011
Novel DNA sensing pathway linked to increased susceptibility to malaria

Scientists at the University of Massachusetts Medical School have uncovered a novel DNA-sensing pathway important to the triggering of an innate immune response for malaria.

Activation of this pathway appears to stimulate production of an overabundance of type-1 interferon by the immune system that may contribute to inflammation and fever in malaria patients and could play a part in susceptibility for the most common and lethal form of malaria known as plasmodium falciparum. Published online by Immunity this week, the study offers the first evidence that recognition of parasite DNA by the innate immune system may play a key role in malaria.

Caused by a parasite transmitted through mosquitoes, malaria is often characterized by successive waves of high fevers, which contribute to the lethalness of the disease and cause many of its complications. The disease initially incubates in liver cells where it can gestate and multiple for up to 30 days. In the second stage, the parasite infects blood cells where it continues to multiply. Invisible to the immune system while inside the blood cells, the malaria parasite periodically bursts through to infect new cells and further multiply. Once the malaria parasite is outside of the blood cells, the immune system is able to detect its presence and attempts to mount a defensive response. It is this response and the corresponding inflammation that accounts for the periodic and deadly waves of fever experienced by malaria patients.

"Traditionally, immunologists have investigated how the adaptive immune system responds to foreign bodies such as virus, bacteria and parasites. It's only over the last 10 to 15 years that we've begun to understand the complex and important role the innate immune system plays in responding to all different classes of pathogens," said Katherine A. Fitzgerald, PhD, associate professor of medicine at UMMS and one of the lead authors of the Immunity study. "In this study, we set out to understand what role the innate immune system plays in this fever response, the dominate symptom found in malaria patients."

Looking at blood samples from febrile malaria patients, Fitzgerald and colleagues found the typical genetic signs expected from patients infected by a pathogen. What they weren't expecting to find, however, were elevated levels of interferon-expressing genes. Typically produced when a virus is detected, interferon triggers the protective defenses of the immune system that can eradicate viruses or tumors. "What we saw when we looked at the samples from malaria patients was a type 1 interferon signature in the immune cells that were responding to the malaria," said Fitzgerald. "This surprised us at the time because traditionally we thought of interferon only in the context of virus infections"

Working with Douglas T. Golenbock, MD, chief of the Division of Infectious Diseases and Immunology at UMMS, Dr. Fitzgerald and colleagues set out to find what was triggering the innate immune response and what effect that response was having on the host cells. What they found was a part of the malaria genome containing a dense portion of the nucleic acids adenine and thymine, two of the building blocks in DNA, which were responsible for activating a novel signaling pathway, including STING, TBK1 and IRF3-IRF7, in the host that enabled innate immune cells to produce type 1 interferon.

When Fitzgerald and colleagues proceeded to test the importance of this pathway to the progression of the disease in small animal models they found another surprise. Those which expressed the normal STING, TBK1 and IRF3-IRF7 pathway all succumbed to the infection within 12 days. However, those that lacked some or all of these genes survived the infection, suggesting that this novel DNA-sensing pathway that leads to type 1 interferon production may play a vital role in the progression of malaria in the host.

"Normally interferon works to eradicate viruses from our body," said Fitzgerald. "In malaria it appears that the interferon response produced by the innate immune system might actually be harmful to the host rather than beneficial. It's not clear yet how or why this occurs but these findings suggest that immune system recognition of DNA and the corresponding production of interferon may play an important role in the parasite's pathogenesis."

Fitzgerald also theorizes that these finding will have broader implications for other infectious and autoimmune diseases. It's possible that with other infectious agents dense portions of the nucleic acids adenine and thymine might also alert the innate immune response to the presence of infection. Additionally, some forms of autoimmunity are associated with overproduction of interferon and it's possible that pathways like those defined here in the context of malaria may be involved in exacerbating these diseases. "More work needs to be done to fully understand these issues" she said.

About the University of Massachusetts Medical School

The University of Massachusetts Medical School (UMMS), one of the fastest growing academic health centers in the country, has built a reputation as a world-class research institution, consistently producing noteworthy advances in clinical and basic research. UMMS attracts more than $255 million in research funding annually, 80 percent of which comes from federal funding sources. The mission of UMMS is to advance the health and well-being of the people of the commonwealth and the world through pioneering education, research, public service and health care delivery with its clinical partner, UMass Memorial Health Care.

Jim Fessenden | EurekAlert!
Further information:
http://www.umassmed.edu

More articles from Health and Medicine:

nachricht Speed data for the brain’s navigation system
06.12.2016 | Deutsches Zentrum für Neurodegenerative Erkrankungen e.V. (DZNE)

nachricht Study suggests possible new target for treating and preventing Alzheimer's
02.12.2016 | Oregon Health & Science University

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Simple processing technique could cut cost of organic PV and wearable electronics

06.12.2016 | Materials Sciences

3-D printed kidney phantoms aid nuclear medicine dosing calibration

06.12.2016 | Medical Engineering

Robot on demand: Mobile machining of aircraft components with high precision

06.12.2016 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>