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Immune system kill switch could be target for chemotherapy and infection recovery
Date:12/6/2012

Researchers have discovered an immune system 'kill switch' that destroys blood stem cells when the body is under severe stress, such as that induced by chemotherapy and systemic infections.

The discovery could have implications for protecting the blood system during chemotherapy or in diseases associated with overwhelming infection, such as sepsis.

The kill switch is triggered when internal immune cell signals that protect the body from infection go haywire. Dr Seth Masters, Dr Motti Gerlic, Dr Benjamin Kile and Dr Ben Croker from the Walter and Eliza Hall Institute led a research project that found blocking these internal signals, in particular a cell receptor called NLRP1, could stop blood stem cells from self-destructing, preventing death after chemotherapy and boosting recovery from infection. The findings were published today in the journal Immunity.

NLRP1 is part of a family of immune receptors that acts as a protective mechanism, instructing immune and blood stem cells to die because it has 'sensed' infection or severe stress-related damage. However this protective mechanism can go too far, Dr Masters said.

"One theory is that when stem cells are infected with a bacteria or virus, they can effectively pass the infection on to all their blood cell offspring, helping to spread the pathogen throughout the body," Dr Masters said. "So the body has evolved to activate this pathway to kill the infected stem cell, reducing the risk of infection. However, in the case of sepsis, or in a cancer patient who contracts an infection, the NLRP1 receptor inappropriately instructs blood stem cells to die, and too many are killed, until the patient can't recover their immune cells, leaving them at much higher risk of death."

Dr Croker said it is the first time that immune receptor-mediated killing of blood stem cells has been suggested to be a critical factor in sepsis, a severe inflammatory disease that kills one person
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Contact: Liz Williams
williams@wehi.edu.au
61-405-279-095
Walter and Eliza Hall Institute
Source:Eurekalert

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