title: Fibrin facilitates both innate and T cell-mediated defense against Yersinia pestis.
abstract: The Gram-negative bacterium Yersinia pestis causes plague, a rapidly progressing and often fatal disease. The formation of fibrin at sites of Y. pestis infection supports innate host defense against plague, perhaps by providing a nondiffusible spatial cue that promotes the accumulation of inflammatory cells expressing fibrin-binding integrins. This report demonstrates that fibrin is an essential component of T cell-mediated defense against plague but can be dispensable for Ab-mediated defense. Genetic or pharmacologic depletion of fibrin abrogated innate and T cell-mediated defense in mice challenged intranasally with Y. pestis. The fibrin-deficient mice displayed reduced survival, increased bacterial burden, and exacerbated hemorrhagic pathology. They also showed fewer neutrophils within infected lung tissue and reduced neutrophil viability at sites of liver infection. Depletion of neutrophils from wild-type mice weakened T cell-mediated defense against plague. The data suggest that T cells combat plague in conjunction with neutrophils, which require help from fibrin to withstand Y. pestis encounters and effectively clear bacteria.
authors.affiliation: Trudeau Institute, Saranac Lake, NY 12983, USA.
authors.forename: Deyan
authors.initials: D
authors.lastname: Luo
authors.forename: Jr-Shiuan
authors.initials: JS
authors.lastname: Lin
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Parent
authors.forename: Isis
authors.initials: I
authors.lastname: Mullarky-Kanevsky
authors.forename: Frank M
authors.initials: FM
authors.lastname: Szaba
authors.forename: Lawrence W
authors.initials: LW
authors.lastname: Kummer
authors.forename: Debra K
authors.initials: DK
authors.lastname: Duso
authors.forename: Michael
authors.initials: M
authors.lastname: Tighe
authors.forename: Jim
authors.initials: J
authors.lastname: Hill
authors.forename: Andras
authors.initials: A
authors.lastname: Gruber
authors.forename: Nigel
authors.initials: N
authors.lastname: Mackman
authors.forename: David
authors.initials: D
authors.lastname: Gailani
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Smiley
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000502:physiology; D005337:Fibrin / Q000502:physiology*; D005340:Fibrinogen / Q000502:physiology; D007113:Immunity, Innate; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010930:Plague / Q000276:immunology / Q000378:metabolism; D010960:Plasminogen Activators / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000382:microbiology*; D015010:Yersinia pestis / Q000276:immunology*
chemical_list: D001426:Bacterial Proteins; D005337:Fibrin; D005340:Fibrinogen; C078140:Pla protease, Yersinia pestis; D010960:Plasminogen Activators