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Originally published online as doi:10.1189/jlb.0503233 on October 13, 2003

Published online before print October 13, 2003
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(Journal of Leukocyte Biology. 2004;75:400-407.)
© 2004 by Society for Leukocyte Biology

Injury, sepsis, and the regulation of Toll-like receptor responses

Thomas J. Murphy, Hugh M. Paterson, John A. Mannick and James A. Lederer1

Department of Surgery, Brigham and Women’s Hospital/Harvard Medical School, Boston, Massachusetts

1 Correspondence: Department of Surgery (Immunology), Brigham and Women’s Hospital, 75 Francis Street, Boston, MA 02115. E-mail: jlederer{at}rics.bwh.harvard.edu

Although we tend to think that the immune system has evolved to protect the host from invading pathogens and to discriminate between self and nonself, there must also be an element of the immune system that has evolved to control the response to tissue injury. Moreover, these potential immune-regulatory pathways controlling the injury response have likely coevolved in concert with self and nonself discriminatory immune-regulatory networks with a similar level of complexity. From a clinical perspective, severe injury upsets normal immune function and can predispose the injured patient to developing life-threatening infectious complications. This remains a significant health care problem that has driven decades of basic and clinical research aimed at defining the functional effects of injury on the immune system. This review and update on our ongoing research efforts addressing the immunological response to injury will highlight some of the most recent advances in our understanding of the impact that severe injury has on the innate and adaptive immune system focusing on phenotypic changes in innate immune cell responses to Toll-like receptor stimulation.

Key Words: innate-immune system • adaptive-immune system • inflammation • SIRS • CARS • cytokines




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