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Type 1 IFN signaling critically regulates influenza-induced alloimmunization to transfused KEL RBCs in a murine model.

Authors
  • Liu, Dong1
  • Gibb, David R1, 2
  • Escamilla-Rivera, Vicente1
  • Liu, Jingchun1
  • Santhanakrishnan, Manjula1
  • Shi, Zhimin1, 3
  • Xu, Lan1
  • Eisenbarth, Stephanie C1, 4
  • Hendrickson, Jeanne E1, 5
  • 1 Department of Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut.
  • 2 Department of Pathology and Laboratory Medicine, Division of Transfusion Medicine, Cedars-Sinai Medical Center, Los Angeles, California.
  • 3 Department of Primary Care, Nanfang Hospital of Southern Medical University, Guangzhou, China. , (China)
  • 4 Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut.
  • 5 Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut.
Type
Published Article
Journal
Transfusion
Publication Date
Oct 01, 2019
Volume
59
Issue
10
Pages
3243–3252
Identifiers
DOI: 10.1111/trf.15482
PMID: 31403208
Source
Medline
Language
English
License
Unknown

Abstract

Only a fraction of red blood cell (RBC) transfusion recipients form alloantibodies, and variables determining responsiveness or nonresponsiveness are poorly understood. We and others have previously shown in animal models that pretreatment with toll-like receptor agonists that mimic different types of infections impacts the magnitude or frequency of RBC alloantibody responses. We hypothesized that influenza infection, coexistent with transfusion, would impact responses to transfused RBCs in a manner dependent on Type 1(α/β) interferon (IFN) signaling and tested this in a murine model. Wild-type mice or mice lacking the ability to respond to Type 1 IFN were infected with influenza prior to the transfusion of transgenic murine RBCs (K1) expressing the human KEL glycoprotein or the triple fusion HOD protein. Alloantibody responses were measured longitudinally after transfusion by flow cytometric crossmatch, and posttransfusion RBC recovery and survival was evaluated. Influenza-infected mice transfused with K1 RBCs developed robust anti-KEL alloantibodies, whereas animals transfused in the absence of infection remained nonresponders; influenza-associated RBC alloimmunization was also observed after transfusion of HOD RBCs. Recipient Type 1 IFN production was critical to the mechanism of action of influenza-induced RBC alloimmunization, with alloimmunization being significantly decreased in mice unable to sense Type 1 IFN (through antibody blockade or genetic approaches). These and other data suggest that Type 1 IFN responses to toll-like receptor agonists or infections regulate RBC alloantibody responses. Studies investigating whether such a correlation exists in humans may be informative. © 2019 AABB.

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