Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Humanized mice may provide clues to better prevent and treat typhoid fever

23.09.2010
The model is based on transplanting human immune stem cells from umbilical blood into mice that are susceptible to infection

Better treatments and prevention for typhoid fever may emerge from a laboratory model that has just been developed for the disease. The model is based on transplanting human immune stem cells from umbilical cord blood into mice that are susceptible to infections.

The transplanted cells live alongside the mouse's own immune system. Although mice are normally resistant to the dangerous strain of Salmonella that causes typhoid fever, the bacteria are able to reproduce in the mice that have received transplanted human cells.

Because typhoid fever affects only humans, progress in creating more effective vaccines and medications has been limited, notes Dr. Ferric C. Fang, professor of laboratory medicine and microbiology at the University of Washington (UW) in Seattle and the senior scientist on the project. The new model enables scientists to study innovative approaches against the disease in a living system, before testing them on people.

The "humanized" mouse model for studying Salmonella typhi infections was reported recently in the Proceedings of the National Academy of Sciences. The lead author of the paper is Stephen J. Libby, research associate professor of laboratory medicine.

The World Health Organization estimates that more than 16,000,000 new cases of typhoid fever occur annually. More than 600,000 people die each year from the disease, which is transmitted through contaminated food or water. Making the situation worse, multi-drug resistant strains have emerged. Researchers are looking for new drugs to replace those that are no longer effective.

The current typhoid fever vaccines have protection rates ranging from 60 to 80 percent. The protection conferred by the present inoculation is short-lived, and doesn't have a booster effect, the researchers explained. The oral vaccine spoils easily if storage conditions aren't optimal – as is the case in many tropical countries where typhoid fever is common. It also requires multiple doses. Studies in travelers suggest that many fail to take the vaccine properly.

Most of what scientists know about how Salmonella causes disease comes from studying a strain called Salmonella typhimurium, which can infect both mice and humans.

However, Fang noted that Salmonella infections in mice have not been found to correlate well with human typhoid infections.

"The mouse Salmonella infection differs from human typhoid in a number of important respects," he said. Immunity to one strain is fundamentally distinct from immunity to the other. This complicates attempts to construct vaccines based on observations of mice infected with Salmonella typhimurium."

Fang added that Salmonella typhi, the cause of human typhoid fever, is highly adapted to people. It has evolved many ways to evade infection-fighting defenses inside humans. It can also enter and destroy disease-fighting cells. The bacteria induce inflammation where it is in their own self-interest, and suppress it when and where it might be a disadvantage, such as in the intestine. Salmonella has changed over time by acquiring new DNA, such as plasmids and bacteriophages, from other organisms. This borrowed DNA makes it more virulent to humans and other animal hosts.

The host-pathogen interactions in mouse typhoid and human typhoid fever are drastically removed from each other, Fang said.

The researchers demonstrated that human blood-forming cells engrafted into immune-deficient mice allowed the mice to be infected with the organism that causes human typhoid fever, and that the typhoid bacteria appeared to reproduce inside the human cells. The researchers were also able to use this model to look for genetic factors that the typhoid bacteria need to cause severe illness.

Based on their studies, the researchers believe that the new lab mouse model can provide an unprecedented opportunity to gain insights into how the human typhoid fever bacterium, Salmonella typhi, causes serious disease and to devise better strategies for the prevention of typhoid fever. Their research also demonstrates how mice engrafted with human stem cells can allow scientists to better understand human infections.

In addition to Fang and Libby, the researchers who collaborated on the model were Kelly Smith, Brad Cookson, Joyce E. Karlinsey, Traci L. Kinkel and Lisa Cummings at the UW School of Medicine, Michael A. Brehm and Dale L. Greiner of the University of Massachusetts School of Medicine; Leonard D. Shultz of The Jackson Laboratory, Bar Harbor, Maine; and Michael McClelland, Steffen Porwollik, and Rocio Canals of the Vaccine Research Institute of San Diego.

The work was supported by the National Institutes of Health, the Diabetes Endocrinology Research Center, the Juvenile Diabetes Research Foundation, and a Beatriu de Pinos fellowship.

Leila Gray | EurekAlert!
Further information:
http://www.washington.edu

More articles from Studies and Analyses:

nachricht New study: How does Europe become a leading player for software and IT services?
03.04.2017 | Fraunhofer-Institut für System- und Innovationsforschung (ISI)

nachricht Reusable carbon nanotubes could be the water filter of the future, says RIT study
30.03.2017 | Rochester Institute of Technology

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

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

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Fighting drug resistant tuberculosis – InfectoGnostics meets MYCO-NET² partners in Peru

28.04.2017 | Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

 
Latest News

Wireless power can drive tiny electronic devices in the GI tract

28.04.2017 | Medical Engineering

Ice cave in Transylvania yields window into region's past

28.04.2017 | Earth Sciences

Nose2Brain – Better Therapy for Multiple Sclerosis

28.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>