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EU-funded team uncover how immune systems take on tuberculosis

A team of EU-funded researchers has discovered a new all-natural technique used by our immune systems to stave off infections. Writing in the journal Cell Host & Microbe, the French, Italian and British researchers show how zinc, a heavy metal that is toxic in high doses, i...

A team of EU-funded researchers has discovered a new all-natural technique used by our immune systems to stave off infections. Writing in the journal Cell Host & Microbe, the French, Italian and British researchers show how zinc, a heavy metal that is toxic in high doses, is used by our immune system cells to destroy microbes like tuberculosis bacillus and Escherichia coli. Their study received EUR 975 999 of funding as part of the 'Molecular markers of M. tuberculosis early interactions with host phagocytes' (MM-TB) project under the 'Life sciences, genomics and biotechnology for health' Thematic area of the EU's Sixth Framework Programme (FP6). The discovery of this new natural defence mechanism against infections has implications for the development of new therapeutic strategies and the testing of new vaccine candidates. It has long been established that to destroy microbes our immune systems deprive them of essential nutrients such as heavy metals like iron. This new study moves forward scientists' knowledge in this area by showing that the process works in the other direction too. Immune cells are also capable of mobilising reserves of heavy metals, especially zinc, to poison microbes. Two microbes the scientists now know are affected by the process are Mycobacterium tuberculosis and E. coli. M. tuberculosis is the agent responsible for tuberculosis in humans, a disease that claims almost 2 million deaths annually worldwide. One third of the world's population is estimated to carry latent infections and the global incidence of tuberculosis increases by 2% annually. Certain strains of E. coli can cause serious infections of the digestive and urinary systems. The researchers note that in immune system cells that had ingested M. tuberculosis or E. coli there was a rapid and persistent accumulation of zinc. They also observed that on the surface of the microbes numerous proteins were produced. Their job was to effectively get rid of heavy metals by acting as 'pumps'. This means that in immune system cells the microbes are exposed to potentially toxic quantities of zinc and they try to protect themselves against intoxication by synthesising these pumping proteins. By inhibiting the pumps through genetic engineering the researchers were able to conclude that M. tuberculosis and E. coli become even more sensitive to destruction by immune system cells. The study shows that although toxic when ingested in too high quantities, zinc can be beneficial for the immune system when it is used by immune system cells to poison microbes. As well as re-opening the dietary supplement debate, these findings could also lead to new antibiotics that would block the action of microbial pumps on metals or to new weakened vaccine strains, which have already been tested as vaccine candidates. Scientists now need to work out whether equivalent mechanisms exist for other heavy metals such as copper. The main aim of the MM-TB project, which ran from 2005 to 2007, was to develop and design new markers of protection and identify unique molecular patterns both in the microbe and in the host cells, associated with early interactions between M. tuberculosis and cells that ingest and destroy foreign particles, bacteria and cell debris. Comparative genomics offers a highly innovative opportunity to decipher M. tuberculosis interactions with the immune system, using transcriptional profiling approaches. In particular, early interactions between M. tuberculosis and host cells are thought to play a crucial role in mounting a protective immune response, and in determining the outcome of infection.For more information, please visit: Centre National de la Recherche Scientifique (CNRS): http://www.cnrs.fr/index.php

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France, Italy, United Kingdom