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An All Important Breakthrough Reached In Understanding T cell response For Parasitic Diseases

Researchers from the University of Georgia have conducted a new study that gives vital information as to how the T cells in the body react to parasitic diseases that affect scores of people every year. //

A study led by scientists at the University of Georgia, that has been just published in the online journal PLOS Pathogens, which is a peer-reviewed, open-access journal published by the Public Library of Science, states that scientists now have a better understanding than ever before on the response of T cells against the parasitic diseases which affect millions each year around the world, killing scores. This study is expected to give some vital information about the diseases caused by parasites, as that has been one area that has remained unclear for scientists who have so far been able to understood how T cells worked in other kinds of diseases.

In the 1980s, the phrase 'T cell count' burst into the world’s medical vocabulary as thousands and then millions of patients died of AIDS. The public began to understand the crucial importance of T cells—cellular Pac-Men that roam the bloodstream gobbling up infection and guarding against future attacks.

'We have needed to really know what happens in these infections,' said Rick Tarleton, research professor of cellular biology and a faculty member in UGA’s Center for Tropical and Emerging Global Diseases (CTEGD). 'What is the body’s response? This study is the first to show that one parasite, Trypanosoma cruzi, which causes Chagas Disease, elicits a T cell response focused on a few peptides, despite having some 12,000 genes capable of generating hundreds of thousands of potential targets for T cells.'

Diana Martin, the lead author and postdoctoral fellow at UGA; former UGA undergraduates Melissa Cabinian and Matthew Crim; computational biologist Brent Weatherly of the CTEGD; former UGA postdoctoral fellow Susan Sullivan; doctoral students Matt Collins, Charles Rosenberg and Sarah Craven; Alessandro Sette of the La Jolla Institute for Allergy and Immunology in San Diego, Ca.; and Susana Laucella and Miriam Postan of the Nacional de Laboratorios e Institutos de Salud in Buenos Aires, Argentina.

Chagas Disease is a tropical parasitic disease that sickens as many as 18 million people a year, mostly in the Americas, and kills 50,000 of those. The parasite that carries it, T. cruzi, is transmitted to mammals and humans through the bite of several genera of flying, biting insects. What intrigued Tarleton was that T cell response to infection from T. cruzi, while important to the body’s ability to fight disease, has remained somewhat cryptic because of the daunting complexity of the processes.

There are actually several kinds of T cells, and the ones Tarleton and his colleagues studied are the cytotoxic T cell, which scientists call CD8+. What they discovered is that the T cell response in T. cruzi is highly focused on a relatively small set of cellular features called 'epitopes,' which are part of a macromolecule that is recognized by the immune system. The specific epitopes involved are ones encoded by the trans-sialidase (or 'ts') family of genes.

'The function of the ts genes is crucial for the parasite,' said Tarleton, 'because the parasite must have sialic acids to invade cells and infect the host. But since it doesn’t have it, it must steal it from the host cells.' The problem is that T. cruzi potentially expresses more than a thousand ts genes, and this pool varies from parasite to parasite—making this set of proteins a poor choice for vaccine development, Tarleton said.

The importance of the new research, however, isn’t in specifically what happens in T. cruzi and Chagas Disease. Rather, it is a new understanding of how T cells react to infection in all parasitic diseases, including malaria, which may cause as many as 500 million infections and three million deaths annually in humans. T he entire area has been little understood because of the almost impenetrable complexity of the problem.

In organisms like viruses and bacteria, which have relatively small genomes, analysis can be more direct; however, understanding the targets of the T cell response in complex pathogens such as T. cruzi requires much more. Scientists must integrate information generated from the recent analysis of the T. cruzi genome and proteome, with bioinformatics and cutting-edge techniques like advanced flow cytometry to unravel what is happening.

Grant support for the research came from the National Institutes of Health.


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