Researchers at the Johns Hopkins Bloomberg School of Public Health have identified a gene in the Anopheles gambiae mosquito’s DNA that is central to the insect’s ability to defend against infectious pathogens, including Plasmodium, the parasite that causes malaria in humans. Potentially, a mosquito with an enhanced capacity to recognize and kill Plasmodium would be unable to transmit malaria. The researchers' findings appear in the June 20, 2006, edition of the journal PLoS Biology.
Insects do not have antibodies, which are essential for pathogen recognition in humans. Instead, insects rely on a limited number of genes coding for adhesive proteins (pattern-recognition receptors) that can adhere to molecular patterns on a pathogen’s surface.
“Each pathogen has its own unique combination of surface patterns. The immune systems of the mosquito and other insects primarily rely on recognizing the pattern of a specific pathogen to activate an immune response that kills the invader,” explained George Dimopoulos, PhD, senior author of the study and assistant professor in the Bloomberg School’s Malaria Research Institute. The AgDscam gene—short for Anopheles gambiae Down syndrome cell adhesion molecule gene—is an essential factor of the mosquito’s immune system and can produce thousands of receptors with different pathogen-binding specificities. AgDscam appears to be capable of recognizing a broad range of different pathogens, and can thereby carry out a function for which a large number of genes would have been needed. Studies previously conducted by other researchers identified an immunity-related function of the Dscam gene in fruit flies.
The researchers found that when the AgDscam gene was deactivated, or “silenced”, the mosquitoes died at a greater rate from bacterial infections. They also found that the numbers of Plasmodium increased 65 percent in the gut of mosquitoes with the silenced gene. The findings suggest that better knowledge of how the AgDscam gene is involved in killing Plasmodium could be used to develop novel ways to control malaria.
The AgDscam gene has 101 protein-coding regions, called exons, that can be spliced together in different combinations to produce over 31,000 possible splice-forms that function as receptors. When the mosquitoes were exposed to different pathogens such as bacteria, fungi and parasites, the AgDscam gene produced an array of different splice-forms with different interaction properties. When the researchers cut AgDscam protein levels in half, they could link AgDscam’s function with the immune system, as the mosquitoes became less resistant to infection. The results showed that infected mosquitoes produced AgDscam splice-forms (receptors) that were better in recognizing—and defending against—the invading pathogen.
“AgDscam is in a way similar to antibodies; different combinations of immunoglobulin domains, which are coded by spliced exons, are used to produce a broad range of receptors. Now we need to learn more about AgDscam’s association with the malaria parasite. A mosquito with an enhanced capacity to recognize and kill Plasmodium would not transmit malaria,” said Dimopoulos.
In a previous study published in the June 8, 2006, edition of PLoS Pathogens, the Hopkins researchers determined that mosquitoes employ the same immune factors to fight off bacterial pathogens as they do to kill malaria-causing Plasmodium parasites.
“AgDscam, a hyper variable immunoglobulin domain containing receptor of the Anopheles gambiae innate immune system” was written by Yuemei Dong, Harry Taylor and George Dimopoulos. Dong and Dimopoulos are with the W. Harry Feinstone Department of Molecular Microbiology and Immunology at the Johns Hopkins Bloomberg School of Public Health. Taylor is currently with Meharry Medical College.
The study was supported by grants from the National Institute of Allergy and Infectious Disease, the World Health Organization Training in Tropical Diseases program, the Ellison Medical Foundation and the Johns Hopkins Malaria Research Institute.
Public Affairs media contacts for the Johns Hopkins Bloomberg School of Public Health: Tim Parsons or Kenna Lowe at 410-955-6878 or email@example.com.
Tim Parsons | EurekAlert!
The birth of a new protein
20.10.2017 | University of Arizona
Building New Moss Factories
20.10.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau
University of Maryland researchers contribute to historic detection of gravitational waves and light created by event
On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...
Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.
Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....
Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).
When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...
Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.
How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...
Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.
It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...
17.10.2017 | Event News
10.10.2017 | Event News
10.10.2017 | Event News
20.10.2017 | Information Technology
20.10.2017 | Materials Sciences
20.10.2017 | Interdisciplinary Research