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 Amputees can learn to control a robotic arm with their minds
28.11.2017 | University of Chicago Medical Center

nachricht The importance of biodiversity in forests could increase due to climate change
17.11.2017 | Deutsches Zentrum für integrative Biodiversitätsforschung (iDiv) Halle-Jena-Leipzig

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: Long-lived storage of a photonic qubit for worldwide teleportation

MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.

Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...

Im Focus: Electromagnetic water cloak eliminates drag and wake

Detailed calculations show water cloaks are feasible with today's technology

Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...

Im Focus: Scientists channel graphene to understand filtration and ion transport into cells

Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.

To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...

Im Focus: Towards data storage at the single molecule level

The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.

Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...

Im Focus: Successful Mechanical Testing of Nanowires

With innovative experiments, researchers at the Helmholtz-Zentrums Geesthacht and the Technical University Hamburg unravel why tiny metallic structures are extremely strong

Light-weight and simultaneously strong – porous metallic nanomaterials promise interesting applications as, for instance, for future aeroplanes with enhanced...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

AKL’18: The opportunities and challenges of digitalization in the laser industry

07.12.2017 | Event News

 
Latest News

A whole-body approach to understanding chemosensory cells

13.12.2017 | Health and Medicine

Water without windows: Capturing water vapor inside an electron microscope

13.12.2017 | Physics and Astronomy

Cellular Self-Digestion Process Triggers Autoimmune Disease

13.12.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>