Fibrin-mediated protection against infection-stimulated immunopathology

J Exp Med. 2003 Mar 17;197(6):801-6. doi: 10.1084/jem.20021493. Epub 2003 Mar 10.

Abstract

Fibrin, a product of the blood coagulation cascade, accompanies many type 1 immune responses, including delayed-type hypersensitivity, autoimmunity, and graft rejection. In those settings, fibrin is thought to exacerbate inflammation and disease. Here, we evaluate roles for coagulation during infection with Toxoplasma gondii, a pathogen whose control requires robust type 1 immunity. We establish that fibrin prevents infection-stimulated blood loss, thereby performing a protective function that is essential for survival. Remarkably, fibrin does not simply protect against vascular damage caused directly by the infectious agent, but rather, protects against hemorrhage evoked by interferon-gamma, a critical mediator of type 1 immunity. This finding, to our knowledge, is the first to document a beneficial role for coagulation during type 1 immunity, and suggests that fibrin deposition protects host tissue from collateral damage caused by the immune system as it combats infection.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blood Coagulation / physiology*
  • Fibrin / genetics
  • Fibrin / immunology
  • Fibrin / metabolism*
  • Immunity / physiology*
  • Interferon-gamma / metabolism
  • Liver / metabolism
  • Liver / parasitology
  • Liver / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Survival Rate
  • Toxoplasma / immunology*
  • Toxoplasmosis / immunology*

Substances

  • Interferon-gamma
  • Fibrin