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Response of Human Liver Tissue to Innate Immune Stimuli.
Wu, Xia; Roberto, Jessica B; Knupp, Allison; Greninger, Alexander L; Truong, Camtu D; Hollingshead, Nicole; Kenerson, Heidi L; Tuefferd, Marianne; Chen, Antony; Koelle, David M; Horton, Helen; Jerome, Keith R; Polyak, Stephen J; Yeung, Raymond S; Crispe, Ian N.
Afiliación
  • Wu X; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, United States.
  • Roberto JB; Department of Medicine, University of Washington, Seattle, WA, United States.
  • Knupp A; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, United States.
  • Greninger AL; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, United States.
  • Truong CD; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, United States.
  • Hollingshead N; Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Institute, Seattle, WA, United States.
  • Kenerson HL; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, United States.
  • Tuefferd M; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, United States.
  • Chen A; Department of Surgery, University of Washington, Seattle, WA, United States.
  • Koelle DM; Infectious Diseases and Vaccines, Janssen Research and Development, Beerse, Belgium.
  • Horton H; Infectious Diseases and Vaccines, Janssen Research and Development, Beerse, Belgium.
  • Jerome KR; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, United States.
  • Polyak SJ; Department of Medicine, University of Washington, Seattle, WA, United States.
  • Yeung RS; Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Institute, Seattle, WA, United States.
  • Crispe IN; Department of Translational Research, Benaroya Research Institute, Seattle, WA, United States.
Front Immunol ; 13: 811551, 2022.
Article en En | MEDLINE | ID: mdl-35355993
Precision-cut human liver slice cultures (PCLS) have become an important alternative immunological platform in preclinical testing. To further evaluate the capacity of PCLS, we investigated the innate immune response to TLR3 agonist (poly-I:C) and TLR4 agonist (LPS) using normal and diseased liver tissue. Pathological liver tissue was obtained from patients with active chronic HCV infection, and patients with former chronic HCV infection cured by recent Direct-Acting Antiviral (DAA) drug therapy. We found that hepatic innate immunity in response to TLR3 and TLR4 agonists was not suppressed but enhanced in the HCV-infected tissue, compared with the healthy controls. Furthermore, despite recent HCV elimination, DAA-cured liver tissue manifested ongoing abnormalities in liver immunity: sustained abnormal immune gene expression in DAA-cured samples was identified in direct ex vivo measurements and in TLR3 and TLR4 stimulation assays. Genes that were up-regulated in chronic HCV-infected liver tissue were mostly characteristic of the non-parenchymal cell compartment. These results demonstrated the utility of PCLS in studying both liver pathology and innate immunity.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Antivirales / Hepatitis C Crónica Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Front Immunol Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Antivirales / Hepatitis C Crónica Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Front Immunol Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza