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Interleukin 10: Protection From Friendly Fire on the Battlefield of Host Defense

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Air date: Wednesday, February 13, 2008, 3:00:00 PM
Time displayed is Eastern Time, Washington DC Local
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Category: Wednesday Afternoon Lectures
Runtime: 00:57:25
Description: Inflammatory tissue damage is the price the body pays for having an immune system to combat microbial invaders. Indeed, in many situations the immunopathology triggered by infection is more detrimental to the host than the direct toxicity caused by the pathogen itself. This paradoxical yet fundamental feature of the anti-infective immune response is often overlooked in analyses of “host resistance” and in the design of immunologic interventions against infectious disease. Interleukin 10 (IL-10) is a cytokine which the body appears to elaborate primarily as a mechanism for keeping immune responses to infection in check thereby preventing collateral tissue damage. It is thus a key element in host protection against microbial agents. Using models of parasitic infection in which CD4+T cells mount highly polarized Th1 or Th2 cytokine responses, we and our colleagues have shown that IL-10 plays a major role in limiting the pathology induced and in preventing mortality. Our studies have also helped delineate a key function for IL-10 in preventing intestinal inflammation against gut dwelling bacteria and in the maintenance of immunologic homeostasis at that site. Finally, in studying the cellular sources of host protective IL-10, our recent work has revealed that IL-10 can be triggered in the same CD4+ T cells that mediate killing of pathogens thus providing a means of self-control of anti-microbial effector responses. Together these observations underscore the critical importance of immunoregulation in host defense and highlight the insights gained from studies on experimental infection models on the mechanisms used by the body to control inflammation.

Alan Sher received his BA from Oberlin College and his Ph.D from the University of California, San Diego under the supervision of Dr. Melvin Cohn at the Salk Institute. After his post-doctoral training at the National Institute for Medical Research, Mill Hill, UK, he served as a Research Associate and later Assistant Professor in the Department of Pathology, Harvard Medical School. He joined the NIAID’s Laboratory of Parasitic Disease as a Section Head in 1980 and became its Chief in 2003. Dr. Sher is the recipient of the Superior Service Award of the USPHS, the Bailey Ashford Award of the American Society of Tropical Medicine and Hygiene, the Bonazinga Award of the Society for Leukocyte Biology and is a member of the American Academy of Microbiology. He is currently an Editor of the Journal of Experimental Medicine and serves on scientific review panels of the Burroughs Wellcome Fund, the Max Planck Institute and the Board of Directors of The Keystone Symposia. Dr. Sher’s work has focused on the immunology of parasitic and bacterial infection and in particular in the regulation and function of polarized CD4+ T cell responses to these pathogens. Much of this work is carried out in vivo in murine experimental models that have been extensively characterized by his group. Dr. Sher’s laboratory has also made important contributions to the field of innate immunity to infection and in pathogen pattern recognition.

The NIH Director's Wednesday Afternoon Lecture Series includes weekly scientific talks by some of the top researchers in the biomedical sciences worldwide.
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NLM Title: Interleukin 10 : protection from friendly fire on the battlefield of host defense [electronic resource] / Alan Sher.
Series: NIH director's Wednesday afternoon lecture series
Author: Sher, Alan.
National Institutes of Health (U.S.)
Publisher:
Other Title(s): NIH director's Wednesday afternoon lecture series
Abstract: (CIT): Inflammatory tissue damage is the price the body pays for having an immune system to combat microbial invaders. Indeed, in many situations the immunopathology triggered by infection is more detrimental to the host than the direct toxicity caused by the pathogen itself. This paradoxical yet fundamental feature of the anti-infective immune response is often overlooked in analyses of "host resistance" and in the design of immunologic interventions against infectious disease. Interleukin 10 (IL-10) is a cytokine which the body appears to elaborate primarily as a mechanism for keeping immune responses to infection in check thereby preventing collateral tissue damage. It is thus a key element in host protection against microbial agents. Using models of parasitic infection in which CD4+T cells mount highly polarized Th1 or Th2 cytokine responses, we and our colleagues have shown that IL-10 plays a major role in limiting the pathology induced and in preventing mortality. Our studies have also helped delineate a key function for IL-10 in preventing intestinal inflammation against gut dwelling bacteria and in the maintenance of immunologic homeostasis at that site. Finally, in studying the cellular sources of host protective IL-10, our recent work has revealed that IL-10 can be triggered in the same CD4+ T cells that mediate killing of pathogens thus providing a means of self-control of anti-microbial effector responses. Together these observations underscore the critical importance of immunoregulation in host defense and highlight the insights gained from studies on experimental infection models on the mechanisms used by the body to control inflammation. Alan Sher received his BA from Oberlin College and his Ph.D from the University of California, San Diego under the supervision of Dr. Melvin Cohn at the Salk Institute. After his post-doctoral training at the National Institute for Medical Research, Mill Hill, UK, he served as a Research Associate and later Assistant Professor in the Department of Pathology, Harvard Medical School. He joined the NIAID's Laboratory of Parasitic Disease as a Section Head in 1980 and became its Chief in 2003. Dr. Sher is the recipient of the Superior Service Award of the USPHS, the Bailey Ashford Award of the American Society of Tropical Medicine and Hygiene, the Bonazinga Award of the Society for Leukocyte Biology and is a member of the American Academy of Microbiology. He is currently an Editor of the Journal of Experimental Medicine and serves on scientific review panels of the Burroughs Wellcome Fund, the Max Planck Institute and the Board of Directors of The Keystone Symposia. Dr. Sher's work has focused on the immunology of parasitic and bacterial infection and in particular in the regulation and function of polarized CD4+ T cell responses to these pathogens. Much of this work is carried out in vivo in murine experimental models that have been extensively characterized by his group. Dr. Sher's laboratory has also made important contributions to the field of innate immunity to infection and in pathogen pattern recognition. The NIH Director's Wednesday Afternoon Lecture Series includes weekly scientific talks by some of the top researchers in the biomedical sciences worldwide.
Subjects: Interleukin-10--immunology
Publication Types: Lectures
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NLM Classification: QW 568
NLM ID: 101469021
CIT Live ID: 6210
Permanent link: http://videocast.nih.gov/launch.asp?14295

 

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