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    Tuesday, 16 July 2013 12:52

    Brain Displays an Intrinsic Mechanism for Fighting Infection

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    White blood cells are reign as the heroes of the immune system. When the infection, the cells produced in the bone marrow, the race through the blood to combat pathogens. But new research shows that different bodies may also play a role in immune defense, which is essentially your own hero. In a study of a rare and deadly brain infection, researchers at Rockefeller University have discovered that the brain cells of healthy people can produce their own immune system molecules, demonstrating the "intrinsic immunity" that is crucial to stop the infection.

    Interfering with interferon Herpes simplex virus-infected neurons

    Interfering with interferon. Herpes simplex virus-infected neurons (above)
    are from patients with a genetic defect that impairs their brain’s ability to make
    interferon, an important immune system protein, and leaves their brain
    cells unable to fight off the infection. Healthy people, in turn,
    have an intrinsic immune response to the virus. (Credit: Image courtesy of Rockefeller University)


    Shen-Ying Zhang, clinical researcher at St. Giles Laboratory of Human Genetics of Infectious Diseases, has been studying children with herpes simplex encephalitis, a potentially deadly brain infection herpes virus, HSV-1, which may be important to brain damage. Scientists already knew from previous work that children with encephalitis have a genetic defect that affects the functions of the immune system receptor - Toll-like receptor 3 (TLR3) - in the brain. For this study we wanted to see how a defect in TLR3 prevent the brain's ability to fight herpes infection.
    When TLR3 recognizes pathogen that causes an immune response that causes the release of proteins known as interferons, and ringing "interfere" with the replication of the pathogen. Most commonly associated with white blood cells that are present within the body, but in this case researchers examines the existence of the receptor in neurons and other brain cells.
    "One interesting thing for these patients is that they have none of the other symptoms, the most frequent herpes. They had an infection of the skin or mouth only in their brains. Therefore hypothesis that TLR3 responses should be specifically responsible for the maintenance of herpes virus infects the brain and is not necessary in other parts of the body, "says Zhang.
    The laboratory, directed by Jean-Laurent Casanova, together with scientists from Harvard Medical School and the Institute of Memorial Sloan-Kettering Cancer to create induced pluripotent stem cells. Made from the patient's own tissue, the stem cells are converted into cells of the central nervous system, which leads to patient genetic defects. Zhang cells exposed to HSV-1 and synthetic double-stranded RNA, which mimics the product of the virus that stimulates Toll-like receptor activity. By measuring the levels of interferon, Zhang revealed that TLR3 response of patients was in fact defective, cells were making these important immune system proteins, preventing them from fighting infection.
    Zhang also exposed to the blood cells of patients with the virus and it was found that TLR3 defect is no problem there, as in the brain - interferons were released in another manner.
    Because Toll-like receptors in neurons was vital to prevent infection, encephalitis, researchers concluded that brain cells use as an internal mechanism to fight infection, rather than relying on the white blood cells. When the function deteriorates, patients who can not be improved.
    "This is proof of intrinsic immunity, recently discovered function of the immune system," says Zhang. "It is very likely that other organs also have their own specific tools to fight infection."
    Researchers are putting together a pilot study to test interferon-based therapy in patients with encephalitis, believing that will help speed recovery and increase survival when used in combination with antiviral drugs. They have also examined whether the brain shows intrinsic immunity to other viral infections.

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