Apr. 29, 2005 Researchers at Yale, in collaboration with NIH researchers, have identified a specific protein molecule that is used by the immune system for detection of parasitic infections, leading the way for development of future vaccines to combat these infections.
Published in the April 28 issue of Science Express, the study provides insight into understanding how infectious parasites interface with the immune system--a problem of great scientific and clinical importance.
Most infections are caused by bacterial or viral microorganisms that produce molecules quite different from those produced by humans and other eukaryotic organisms. When microorganisms infect humans, the atypical molecules are usually detected immediately by human proteins called Toll-like receptors (TLR) that alert the human immune system to fight the infection.
But parasites, like humans, are eukaryotic in origin and how the body detects them has been a mystery.
The common parasite Toxoplasma gondii (T. gondii) causing toxoplasmosis, has a complicated life cycle in which it is transmitted from mice to cats and then to humans. Previous research had shown that T. gondii is recognized by a TLR and that the recognition of this parasite is crucial for an appropriate immune response. However, it was unclear which of the 13 different TLRs present in mammals was responsible and which molecule of T. gondii was being recognized by the TLRs.
"In this study we found that the recognition of T. gondii by the innate immune system is mediated by a new member of the TLR family, TLR 11, that we discovered last year," said Sankar Ghosh, professor of immunobiology at Yale School of Medicine. "We further found that the specific recognition molecule was Toxoplasma profilin. The innate immune system has the capacity to recognize these proteins and the profilins are the triggers."
Ghosh said that although parasitic infections are less prominent in the United States than bacterial and viral infections, the global impact of parasitic infections on health is tremendous. "Insight obtained from these studies should lead to development of novel strategies to combat these infections," he said. "In particular, an understanding of the parasite components that trigger a host immune response may facilitate the development of better vaccines."
Other authors from Yale are Dekai Zhang, Matthew S. Hayden, Fayyaz S. Sutterwala and Richard A. Flavell.
The research was funded by National Institutes of Health.
Citation: Science Express (10.1126/science.1109893) (April 28, 2005).
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