Fibrin-mediated protection against infection-stimulated immunopathology.
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.
Johnson
Lawrence L
LL
Trudeau Institute, Saranac Lake, NY 12983, USA.
Berggren
Kiera N
KN
Szaba
Frank M
FM
Chen
Wangxue
W
Smiley
Stephen T
ST
D000818:Animals; D001777:Blood Coagulation / Q000502:physiology*; D005337:Fibrin / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007109:Immunity / Q000502:physiology*; D007371:Interferon-gamma / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015996:Survival Rate; D014122:Toxoplasma / Q000276:immunology*; D014123:Toxoplasmosis / Q000276:immunology*
D007371:Interferon-gamma; D005337:Fibrin