Parasite evades death by promoting host cell survival

Dec 08, 2009
A human cell infected with Trypanosoma cruzi. Akt kinase (shown in purple) activates PDNF (shown in green) on the parasite surface. Credit: Tufts University

Researchers have discovered how the parasite Trypanosoma cruzi, which causes Chagas' disease, prolongs its survival in infected cells. A protein on the parasite activates the enzyme Akt, which blocks cell death signals, preventing cell destruction and parasite elimination. Chagas' disease affects some 8 to 11 million people throughout Latin America and even the United States.

The parasite Trypanosoma cruzi (or T. cruzi), which causes Chagas' disease, will go to great lengths to evade death once it has infected human host cells, researchers have discovered. In a study published in the November 17 online issue of Science Signaling, the researchers describe how a protein called parasite-derived neurotrophic factor (PDNF) prolongs the life of the T. cruzi parasite by activating anti-apoptotic (or anti-cell-death) molecules in the host cell. These protective mechanisms help to explain how host cells continue to survive despite being exploited by T. cruzi .

"We asked ourselves, 'How is it possible that the host cells stay alive for so long with thousands of T. cruzi parasites consuming the host cell's vital resources?' We discovered that PDNF on the surface of the T. cruzi parasite essentially inhibits cell death signals and activates cell-protective mechanisms, ensuring T. cruzi sufficient time to develop and reproduce in the ," says senior author Mercio Perrin, MD, PhD, professor in the pathology department at Tufts University School of Medicine (TUSM) and member of the immunology program faculty at the Sackler School of Graduate Biomedical Sciences at Tufts.

Taking a multi-faceted approach, the researchers used bioinformatics, immunochemistry, intracellular colocalization microscopy, and in vitro enzymatic techniques to study T. cruzi survival in the host. Perrin and co-author Marina Chuenkova, PhD, a research instructor in the pathology department at TUSM and the Sackler School, demonstrated that PDNF is a substrate and activator of Akt kinase, an enzyme that promotes cell survival by inhibiting "cell death" proteins.

"Further investigation showed that within T. cruzi-infected cells, PDNF also activates increased production of Akt, prolonging its protective effects," says Chuenkova. "Akt is a key regulator of diverse cellular processes, and supports cell survival not only by inhibiting apoptotic molecules, but additionally by increasing nutrient uptake and metabolism," she continued.

"In short, the T. cruzi parasite has a means of establishing life insurance once it has invaded the host. If we can fully understand the mechanisms behind this protection, we can begin to explore ways to undermine it with treatment," said Perrin.

Chagas' disease, typically transmitted to humans by blood-feeding insects, infects an estimated 8 to 11 million people throughout Mexico, and Central and South America. Although it is still rare in the United States, according to the Centers for Disease Control and Prevention (CDC), there are 300,000 people with Chagas' disease living in the United States, most of whom acquired the disease while living in other countries.

The acute phase of Chagas' disease can result in fever or swelling at the site of the insect bite, but many people do not experience symptoms at all. If left untreated, the disease enters an indeterminate phase in which no symptoms are present. During this phase, many people are not aware that they are infected, but approximately 30 percent will eventually develop life-threatening complications of the disease, including enlargement of the digestive tract and/or heart.

More information: Chuenkova MV and PereiraPerrin M. Science Signaling. 2009. (November 17); 2(97), ra74. "Trypanosoma cruzi targets Akt in host cells as an intracellular antiapoptotic strategy." Published online November 17, 2009, doi:10.1126/scisignal.2000374

Source: Tufts University

Explore further: Structure of sodium channels different than previously believed

add to favorites email to friend print save as pdf

Related Stories

Toxoplasmosis infection trick revealed by scientists

May 10, 2007

Toxoplasmosis is a parasitic disease, primarily carried by cats. It is transmitted to humans by eating undercooked meat or through contact with cat faeces. It is particularly dangerous for pregnant women, whose foetuses can ...

How Toxoplasma gondii gets noticed

Jan 19, 2009

Researchers provide insight into how Toxoplasma gondii, a common parasite of people and other animals, triggers an immune response in its host. The report will appear online on January 19th in The Journal of Experimental Medicine. ...

Recommended for you

Breakthrough points to new drugs from nature

Apr 16, 2014

Researchers at Griffith University's Eskitis Institute have developed a new technique for discovering natural compounds which could form the basis of novel therapeutic drugs.

World's first successful visualisation of key coenzyme

Apr 16, 2014

Japanese researchers have successfully developed the world's first imaging method for visualising the behaviour of nicotine-adenine dinucleotide derivative (NAD(P)H), a key coenzyme, inside cells. This feat ...

User comments : 0

More news stories

Impact glass stores biodata for millions of years

(Phys.org) —Bits of plant life encapsulated in molten glass by asteroid and comet impacts millions of years ago give geologists information about climate and life forms on the ancient Earth. Scientists ...

Researchers successfully clone adult human stem cells

(Phys.org) —An international team of researchers, led by Robert Lanza, of Advanced Cell Technology, has announced that they have performed the first successful cloning of adult human skin cells into stem ...