Innate and Adaptive Immunity to Transfused Allogeneic RBCs in Mice Requires MyD88

Arielle Soldatenko, Laura R. Hoyt, Lan Xu, Samuele Calabro, Steven M. Lewis, Antonia E. Gallman, Krystalyn E. Hudson, Sean R. Stowell, Chance J. Luckey, James C. Zimring, Dong Liu, Manjula Santhanakrishnan, Jeanne E. Hendrickson, Stephanie C. Eisenbarth

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

RBC transfusion therapy is essential for the treatment of anemia. A serious complication of transfusion is the development of non-ABO alloantibodies to polymorphic RBC Ags; yet, mechanisms of alloantibody formation remain unclear. Storage of mouse RBCs before transfusion increases RBC immunogenicity through an unknown mechanism. We previously reported that sterile, stored mouse RBCs activate splenic dendritic cells (DCs), which are required for alloimmunization. Here we transfused mice with allogeneic RBCs to test whether stored RBCs activate pattern recognition receptors (PRRs) on recipient DCs to induce adaptive immunity. TLRs are a class of PRRs that regulate DC activation, which signal through two adapter molecules: MyD88 and TRIF. We show that the inflammatory cytokine response, DC activation and migration, and the subsequent alloantibody response to transfused RBCs require MyD88 but not TRIF, suggesting that a restricted set of PRRs are responsible for sensing RBCs and triggering alloimmunization.

Original languageEnglish (US)
Pages (from-to)991-997
Number of pages7
JournalJournal of Immunology
Volume208
Issue number4
DOIs
StatePublished - Feb 15 2022
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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